Ammonium Chloride → tert-butyl (2R)-2-(tert-butyldimethylsilyloxy)-4-(3-fluorophenyl)-4-hydroxybutylcarbamate

HRID 513003ノート

反応式

HRID 513003 の反応式
[Si:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:11](=[O:21])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:22][C:23]1[CH:24]=[C:25]([Mg]Br)[CH:26]=[CH:27][CH:28]=1.[BH4-].[Na+].[NH4+].[Cl-]>C1COCC1.CO>[Si:1]([O:8][C@H:9]([CH2:10][CH:11]([C:27]1[CH:26]=[CH:25][CH:24]=[C:23]([F:22])[CH:28]=1)[OH:21])[CH2:13][NH:12][C:14](=[O:15])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 11220792(R)-1-Boc-4-[(tert-butyldimethylsilyl)oxy]pyrrolidin-2-oneHCID 178505773HCID 178505773、化合物

生成物 1

HCID 66684244tert-butyl (2R)-2-(tert-butyldimethylsilyloxy)-4-(3-fluorophenyl)-4-hydroxybutylcarbamate

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of (R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-oxopyrrolidine-1-carboxylate (I-1) (13.6 g, 43.2 mmol) in THF (100 mL) at 0° C. under N2 was added (3-fluorophenyl)magnesium bromide (52 mL of 1 M solution in THF, 51.84 mmol) over 1 hour. The reaction mixture was stirred at 0° C. for 1 hour. Methanol (80 mL) was added to the mixture followed by NaBH4 (2.45 g, 64.8 mmol) at 0° C. The mixture was stirred at 0° C. for 1 hour then poured into 10% aqueous NH4Cl. The mixture was extracted with EtOAc, washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield tert-butyl (2R)-2-(tert-butyldimethylsilyloxy)-4-(3-fluorophenyl)-4-hydroxybutylcarbamate (I-2). 1H NMR (400 MHz, CDCl3) δ 7.33-7.28 (m, 1 H), 7.13-7.09 (m, 2 H), 6.98-6.92 (m, 1 H), 4.97-4.90 (m, 1 H), 4.82 (bs, 1 H), 4.12-4.06 (m, 1 H), 3.42-3.33 (m, 1 H), 3.22-3.17 (m, 1 H), 1.88-1.84 (m, 2 H), 1.47 (s, 9 H), 0.93 (s, 9 H), 0.11 (s, 6 H). MS m/z 436.1 (M+23)+.

後処理

  1. stirringThe mixture was stirred at 0° C. for 1 hour
  2. extractionThe mixture was extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant

出典と根拠

ORDレコード
ord-6bdf280a01c549f3a51333b916093385
出典データセット
uspto-grants-2015_08
特許番号
US09102671B2

反応ノート

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