反応 #52157

反応方程式

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

MeI

LDA

→

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

溶媒

THF

反応条件

後処理

1. 1
   温度The reaction was cooled to −30° C.
2. 2
   その他was quenched with saturated aqueous ammonium chloride (50 mL)
3. 3
   その他The resulting mixture was partitioned between EtOAc and brine
4. 4
   抽出the product was extracted with EtOAc (3×100 mL)
5. 5
   乾燥The combined extracts were dried over anhydrous MgSO4
6. 6
   濃縮concentrated in vacuo
7. 7
   その他The solvent was removed in vacuo
8. 8
   その他the residue was purified by repeated flash column chromatography on silica gel
9. 9
   洗浄eluted with 20:1 to 10:1 hexane/acetone

実験手順

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).

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