تفاعل #615138

معادلة التفاعل

NH4Cl

n-BuLi

benzyl chloroformate

CO2

(S)-glycidyl butyrate

Cs2CO3

3-fluoro-4-methyl-aniline

NaHCO3

→

title intermediate

المردود 53.0%

(S)-3-(3-fluoro-4-methyl-phenyl)-5-hydroxymethyl-oxazolidin-2-one

المردود 53.0%

المذيبات

EA

acetone

ظروف التفاعل

المعالجة

1. 1
   أخرىthe mixture was partitioned between EA and sat. aq. NaHCO3
2. 2
   تجفيفlayer was dried over MgSO4
3. 3
   تركيزconcentrated under reduced pressure
4. 4
   workup.DISSOLUTIONThe resulting benzyl carbamate was dissolved in THF (50 mL)
5. 5
   workup.ADDITIONwas added dropwise
6. 6
   workup.ADDITIONwas added dropwise
7. 7
   workup.STIRRINGThe mixture was stirred at rt overnight
8. 8
   workup.STIRRINGthe mixture was stirred at rt for 3 h
9. 9
   أخرىthe phases were separated
10. 10
    استخلاصThe aq. phase was extracted once more with EA
11. 11
    غسيلextracts were washed several times with sat. aq. NH4Cl
12. 12
    تجفيفwith brine, dried over Na2SO4
13. 13
    تركيزconcentrated
14. 14
    أخرىThe orange solid obtained
15. 15
    أخرىwas triturated with EA

الإجراء التجريبي

A mixture of 3-fluoro-4-methyl-aniline (commercial; 1.25 g, 10 mmol), sat. aq. NaHCO3 (10 mL) and acetone (10 mL) was treated dropwise with benzyl chloroformate (1.70 g, 1.41 mL, 1 eq.). After CO2 evolution ceased, the mixture was partitioned between EA and sat. aq. NaHCO3, the org. layer was dried over MgSO4 and concentrated under reduced pressure. The resulting benzyl carbamate was dissolved in THF (50 mL) and cooled under argon to −78° C. n-BuLi (2.5M in Hex, 6.45 mL, 1.1 eq.) was added dropwise, and the resulting solution was stirred for 1 h at that temperature. The reaction was then allowed to warm to −15° C. at which (S)-glycidyl butyrate (1.69 mL, 1.1 eq.) was added dropwise. The mixture was stirred at rt overnight. A tip of a spatula of Cs2CO3 was added, and the mixture was stirred at rt for 3 h. NH4Cl and EA were added and the phases were separated. The aq. phase was extracted once more with EA and the combined org. extracts were washed several times with sat. aq. NH4Cl, then with brine, dried over Na2SO4 and concentrated. The orange solid obtained was triturated with EA to afford the title intermediate as a pale yellow solid (1.18 g, 53% yield).

المصدر