Lithium triethylborohydride → (2S,3S)-3-(Boc)amino-4-(5-bromothiazol-2-yl(Boc)amino)-2-(4-(trifluoromethyl)phenyl)butan-1-ol

HRID 661094ノート

反応式

HRID 661094 の反応式
C([O:7][CH2:8][C@@H:9]([C:34]1[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=1)[C@H:10]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:11][N:12]([C:20]1[S:21][C:22]([Br:25])=[CH:23][N:24]=1)[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])(=O)C(C)(C)C.[Li+].[B-](CC)(CC)CC>C1COCC1>[C:27]([NH:26][C@H:10]([CH2:11][N:12]([C:20]1[S:21][C:22]([Br:25])=[CH:23][N:24]=1)[C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[C@H:9]([C:34]1[CH:39]=[CH:38][C:37]([C:40]([F:41])([F:42])[F:43])=[CH:36][CH:35]=1)[CH2:8][OH:7])([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28]

参加物

4

反応物 2

HCID 23712863Lithium triethylborohydrideHCID 57633960(2S,3S)-3-(Boc)amino-4-(5-bromothiazol-2-yl(Boc)amino)-2-(4-(trifluoromethyl)phenyl)butyl pivalate

生成物 1

HCID 57634162(2S,3S)-3-(Boc)amino-4-(5-bromothiazol-2-yl(Boc)amino)-2-(4-(trifluoromethyl)phenyl)butan-1-ol収率 88%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

(2S,3S)-3-(Boc)amino-4-(5-bromothiazol-2-yl(Boc)amino)-2-(4-(trifluoromethyl)phenyl)butyl pivalate (0.66 g, 0.95 mmol) was taken up in 10 mL of THF and chilled to −78° C. Super hydride, 1M in THF (2.4 mL, 2.4 mmol) was added. The mixture was stirred for 5 minutes and then warmed to 0° C. The mixture was stirred for 15 minutes and then quenched with 5 mL of EtOAc. The mixture was diluted with 10 mL of aqueous NH4Cl and partitioned in a separatory funnel. The aqueous portion was extracted twice with 20 mL of EtOAc, and the combined organic layers were washed with 10 mL of brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (5% to 25% EtOAc/hexanes) afforded (2S,3S)-3-(Boc)amino-4-(5-bromothiazol-2-yl(Boc)amino)-2-(4-(trifluoromethyl)phenyl)butan-1-ol (0.51 g, 88% yield) 82646-5-1 as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.61 (d, J=8.02 Hz, 2H) 7.35 (d, J=8.02 Hz, 2H) 5.16-5.02 (m, 1H) 4.60-4.51 (m, 1H), 4.33-4.20 (m 1H) 4.09-3.96 (m, 1H), 3.91-3.65 (m, 2H) 3.15-3.05 (m, 1H) 1.52 (s, 9H) 1.37 (s, 9H).

後処理

  1. temperaturewarmed to 0° C
  2. stirringThe mixture was stirred for 15 minutes
  3. customquenched with 5 mL of EtOAc
  4. additionThe mixture was diluted with 10 mL of aqueous NH4Cl
  5. custompartitioned in a separatory funnel
  6. extractionThe aqueous portion was extracted twice with 20 mL of EtOAc
  7. washthe combined organic layers were washed with 10 mL of brine
  8. dry with materialdried over MgSO4
  9. filtrationFiltration and concentration under reduced pressure

出典と根拠

ORDレコード
ord-8c483efb39474cbd96a054f8288861df
出典データセット
uspto-grants-2011_12
特許番号
US08084479B2

反応ノート

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