Sodium Carbonate → Tert-butyl 3-(3,4-difluorophenyl)-3-hydroxypyrrolidine-1-carboxylate

HRID 1931882노트

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HRID 1931882 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([F:9])[CH:3]=1.C([Li])CCC.[C:15]([N:22]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23]1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)C>[F:9][C:4]1[CH:3]=[C:2]([C:24]2([OH:27])[CH2:25][CH2:26][N:22]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:23]2)[CH:7]=[CH:6][C:5]=1[F:8]

참가 물질

6

반응물 4

HCID 10340Sodium CarbonateHCID 676754-Bromo-1,2-difluorobenzeneHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 67405004Tert-butyl 3-(3,4-difluorophenyl)-3-hydroxypyrrolidine-1-carboxylate수율 47.9%

시약·촉매·용매 1

HCID 3283Diethyl Ether용매2회

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온도
-78 °C

실험 절차

To a solution of 1-bromo-3,4-difluorobenzene (3.5 g, 18.13 mmol) in dry diethyl ether (25 mL) under nitrogen at −78° C., was added dropwise n-butyllithium (2.5 M in hexane, 7.25 mL, 18.13 mmol). The mixture was stirred for 30 min at −78° C. after which a solution of 1-N-boc-3-pyrrolidinone (3.35 g, 18.13 mmol) in dry diethyl ether (25 mL) was added drop wise. The mixture was stirred at −78° C. for 10 min and then brought to ambient temperature over a period of 2 h. Aqueous sodium carbonate (10%) was added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated. Purification by flash column chromatography on silica gel (isooctane/ethyl acetate, 4:1 to 1:1) gave the title compound (2.6 g). MS m/z (rel. intensity, 70 eV) 243 (18), 198 (23), 141 (18), 127 (21), 57 (bp).

후처리

  1. additionwas added drop wise
  2. waitbrought to ambient temperature over a period of 2 h
  3. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  4. dry with materialThe combined organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by flash column chromatography on silica gel (isooctane/ethyl acetate, 4:1 to 1:1)

출처 및 근거

ORD 기록
ord-32ff9a71ab6a4741824a66bba928f680
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188301B2

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