تفاعل #79842

معادلة التفاعل

4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-cyclohexanone

diisopropylamine

n-butyl lithium

acetonitrile

→

4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-hydroxycyclohexylmethyl cyanide

المذيبات

tetrahydrofuran

hexamethylphosphoramide

tetrahydrofuran

—

hexanes

ظروف التفاعل

المعالجة

1. 1
   أخرىthe temperature less than 5° C
2. 2
   workup.ADDITIONAfter the addition
3. 3
   درجة الحرارةThe mixture was cooled to −78° C.
4. 4
   أخرىthe temperature less than −70° C
5. 5
   workup.ADDITIONAfter the addition
6. 6
   workup.STIRRINGthe mixture was stirred for 20 minutes at −78° C.
7. 7
   workup.ADDITIONwas added
8. 8
   أخرىthe temperature less than −70° C
9. 9
   workup.ADDITIONAfter the addition
10. 10
    workup.STIRRINGthe mixture was stirred for 30 minutes at −78° C.
11. 11
    workup.STIRRINGstirred at ambient temperature for 18 hours
12. 12
    أخرىThe mixture was partitioned between dichloromethane and saturated ammonium chloride (aq)
13. 13
    غسيلThe organic phase was washed with water and saturated sodium bicarbonate (aq)
14. 14
    تجفيفdried over magnesium sulfate
15. 15
    أخرىThe solvent was removed in vacuo
16. 16
    أخرىthe cis and trans isomers were separated by flash column chromatography on silica

الإجراء التجريبي

A solution of diisopropylamine (0.649 g, 0.0050 mol) in tetrahydrofuran (10 mL) was cooled to 0° C. A solution of 1.6 M n-butyl lithium (3.14 mL, 0.0050 mol) in hexanes was added dropwise, keeping the temperature less than 5° C. After the addition was complete, the mixture was stirred for 20 minutes at 0° C. The mixture was cooled to −78° C., and dry acetonitrile (0.175 g, 0.0043 mol) was added, keeping the temperature less than −70° C. After the addition was complete, the mixture was stirred for 20 minutes at −78° C., and a mixture of 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-cyclohexanone (1.000 g, 0.0025 mmol) in tetrahydrofuran (10 mL) and hexamethylphosphoramide (10 mL) was added, keeping the temperature less than −70° C. After the addition was complete, the mixture was stirred for 30 minutes at −78° C., then stirred at ambient temperature for 18 hours. The mixture was partitioned between dichloromethane and saturated ammonium chloride (aq). The organic phase was washed with water and saturated sodium bicarbonate (aq), and dried over magnesium sulfate. The solvent was removed in vacuo and the cis and trans isomers were separated by flash column chromatography on silica using dichloromethane/methanol (95:5) as an eluent to give less polar 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-hydroxycyclohexylmethyl cyanide (0.120 g, 0.00027 mol) and more polar 4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-hydroxycyclohexylmethyl cyanide (0.170 g, 0.00038 mol):

المصدر