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

HRID 513003노트

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HRID 513003 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-6bdf280a01c549f3a51333b916093385
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102671B2

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