Ammonium Chloride → 1-Benzyl-3-(3-chloro-2-fluorophenyl)pyrrolidin-3-ol

HRID 1931888

반응식

HRID 1931888 반응식
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[F:9].C([Li])CCC.[CH2:15]([N:22]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[Cl-].[NH4+]>C(OCC)C>[CH2:15]([N:22]1[CH2:26][CH2:25][C:24]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=2[F:9])([OH:27])[CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

참가 물질

6

반응물 4

HCID 25517Ammonium ChlorideHCID 698901-Benzyl-3-pyrrolidinoneHCID 36857621-Bromo-3-chloro-2-fluorobenzeneHCID 178418339Butyllithium

생성물 1

HCID 685157901-Benzyl-3-(3-chloro-2-fluorophenyl)pyrrolidin-3-ol수율 92.9%

시약·촉매·용매 1

HCID 3283Diethyl Ether용매2회

실험 절차

To a solution of 1-bromo-3-chloro-2-fluorobenzene (11.8 g, 56.3 mmol) in dry diethyl ether (100 mL), under nitrogen at −78° C. was added drop wise n-butyllithium (2.5 M in hexane, 22.5 mL, 56.3 mmol). The mixture was stirred at −78° C. for 10 min after which a solution of 1-benzylpyrrolidin-3-one (10 g, 56.3 mmol) in dry diethyl ether (50 mL) was added drop wise. The resulting mixture was brought to ambient temperature, aqueous ammonium chloride solution (50%, 50 mL) was added and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic phase was dried (MgSO4), filtered and evaporated. Purification by flash chromatography on silica gel (isooctane/ethyl acetate, 1:1) gave the title compound (16 g). MS m/z (relative intensity, 70 eV) 305 (M+, 9), 214 (41), 133 (71), 132 (50), 91 (bp).

후처리

  1. additionwas added drop wise
  2. customwas brought to ambient temperature
  3. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  4. dry with materialThe combined organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by flash chromatography on silica gel (isooctane/ethyl acetate, 1:1)

출처 및 근거

ORD 기록
ord-85ed1e5d2eb643a6b63018a8c639e2a3
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188301B2

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