반응 #52157

반응 방정식

N-BOC-4(R)-hydroxyproline, methyl ester

MeI

LDA

→

N-BOC-4(R)-hydroxy-2-methyl-(L)-proline, methyl ester

용매

THF

반응 조건

후처리

1. 1
   온도The reaction was cooled to −30° C.
2. 2
   기타was quenched with saturated aqueous ammonium chloride (50 mL)
3. 3
   기타The resulting mixture was partitioned between EtOAc and brine
4. 4
   추출the product was extracted with EtOAc (3×100 mL)
5. 5
   건조The combined extracts were dried over anhydrous MgSO4
6. 6
   농축concentrated in vacuo
7. 7
   기타The solvent was removed in vacuo
8. 8
   기타the residue was purified by repeated flash column chromatography on silica gel
9. 9
   세척eluted with 20:1 to 10:1 hexane/acetone

실험 절차

To a solution of N-BOC-4(R)-hydroxyproline, methyl ester (Bachem, 17 g, 69 mmol) and MeI (276 mmol) in 250 mL of anhydrous THF at −30° C. was added LDA (Aldrich, 1.5 M in cyclohexane, 250 mmol). The reaction was allowed to warm up to rt over 4 h. The reaction was cooled to −30° C., and was quenched with saturated aqueous ammonium chloride (50 mL). The resulting mixture was partitioned between EtOAc and brine, and the product was extracted with EtOAc (3×100 mL). The combined extracts were dried over anhydrous MgSO4 and concentrated in vacuo. The solvent was removed in vacuo and the residue was purified by repeated flash column chromatography on silica gel eluted with 20:1 to 10:1 hexane/acetone to afford N-BOC-4(R)-hydroxy-2-methyl-(L)-proline, methyl ester (slower eluting and major isomer, 10 g, 58%). The stereochemistry was assigned by NMR comparisons with literature reports (Noe, C R et al Pharmazie 1996, 51, 800).

출처