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

HRID 2109767노트

반응식

HRID 2109767 반응식
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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

(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).

후처리

  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

출처 및 근거

ORD 기록
ord-91fd50582db84bb98afcc8674cb9d718
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07514566B2

반응 노트

불러오는 중…