반응 #90196

반응 방정식

3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one

tris(o-tolyl)phosphine

sodium borohydride

DBU

ethyl chloroformate

→

solid

수율 8.3%

8-((R)-2,3-Dihydroxy-propoxy)-3-hydroxymethyl-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

수율 8.3%

용매

THF

ethanol

ethanol

THF

반응 조건

후처리

1. 1
   기타irradiation at 160° C. for 15 min under nitrogen atmosphere
2. 2
   기타The resulting reaction solution
3. 3
   기타was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate
4. 4
   세척The organic layer was washed with saturated brine
5. 5
   농축concentrated under reduced pressure
6. 6
   workup.DISSOLUTIONThe resulting residues were dissolved in ethanol (10 ml)
7. 7
   workup.ADDITIONTHF (3 ml), added with 2 N KOH (2 ml)
8. 8
   기타The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate
9. 9
   세척The organic layer was washed with saturated brine
10. 10
    농축concentrated under reduced pressure
11. 11
    기타purified with MTBE/hexane (1/1) (155.4 mg)
12. 12
    workup.STIRRINGthe mixture was stirred at 0° C. for 2 hrs
13. 13
    workup.STIRRINGwas then stirred at room temperature for 2 hrs
14. 14
    기타The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate
15. 15
    세척The organic layer was washed with saturated brine
16. 16
    농축concentrated under reduced pressure
17. 17
    기타The resulting residues were purified by silica gel column (MeOH/DCM) (35.2 mg)

실험 절차

3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one (200.2 mg, 0.426 mmol), palladium acetate (II) (19 mg, 0.0848 mmol), hexacarbonyl molybdenum (115.5 mg, 0.438 mmol) and tris(o-tolyl)phosphine (52.5 mg, 0.172 mmol) were dissolved in THF (1.3 ml) and ethanol (0.075 ml), added with DBU (0.195 ml), and subjected to microwave irradiation at 160° C. for 15 min under nitrogen atmosphere. The resulting reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were dissolved in ethanol (10 ml) and THF (3 ml), added with 2 N KOH (2 ml), and stirred at room temperature for 2 hrs, at 50° C. overnight and at 70° C. for 2 hrs. The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were suspended and purified with MTBE/hexane (1/1) (155.4 mg). The THF solution (1.5 ml) of the product (109 mg) was added with TEA (0.052 ml, 0.373 mmol) and ethyl chloroformate (0.029 ml, 0.303 mmol) under ice cooling, and the mixture was stirred at 0° C. for 2 hrs. Subsequently, ethanol (1 ml) and sodium borohydride (75.7 mg, 2.0 mmol) were added to the mixture, which was then stirred at room temperature for 2 hrs. The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (MeOH/DCM) (35.2 mg). Thus-obtained solid (9.6 mg) was dissolved in MeOH (1 ml), added with 1 N HCl (3 drops), and the mixture was stirred at 60° C. for 90 min. After cooling and concentration under reduced pressure, the resultant was purified by TLC (MeOH/DCM) to obtain Compound GT20-8 (6.2 mg, white solid) and Compound GT20-9 (4.3 mg, white solid).

출처