Ammonium Chloride → 1-Benzyl-3-(2,3-difluorophenyl)pyrrolidin-3-ol

HRID 1931886ノート

反応式

HRID 1931886 の反応式
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F: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]([F: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

参加物

6

反応物 4

HCID 25517Ammonium ChlorideHCID 698901-Benzyl-3-pyrrolidinoneHCID 27332601-Bromo-2,3-difluorobenzeneHCID 178418339Butyllithium

生成物 1

HCID 685158491-Benzyl-3-(2,3-difluorophenyl)pyrrolidin-3-ol収率 57.9%

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of 1-bromo-2,3-difluorobenzene (25 g, 129.5 mmol) in dry diethyl ether (150 mL), under nitrogen at −78° C. was added drop wise n-butyllithium (2.5 M in hexane, 51.8 mL, 129.5 mmol). The mixture was stirred for 30 min after which a solution of 1-benzylpyrrolidin-3-one (20.4 g, 116.5 mmol) in dry diethyl ether (50 mL) was added drop wise. The mixture was stirred at −78° C. for 30 min and for 2 h at ambient temperature. Aqueous saturated ammonium chloride solution (50 mL) was added and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (isooctane/ethyl acetate/triethyl amine, 75:20:5) gave the title compound (19.5 g). MS m/z (relative intensity, 70 eV) 289 (M+, 20), 198 (69), 133 (72), 132 (51), 91 (bp).

後処理

  1. additionwas added drop wise
  2. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by flash chromatography on silica gel (isooctane/ethyl acetate/triethyl amine, 75:20:5)

出典と根拠

ORDレコード
ord-f4a3e1d074624c32b30b650cff58fd11
出典データセット
uspto-grants-2012_05
特許番号
US08188301B2

反応ノート

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