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

HRID 2109767Notes

Reaction equation

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]

Participants

Conditions

Temperature: -78 °C

Procedure

(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).

Workup

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

Sources & evidence

ORD record: ord-91fd50582db84bb98afcc8674cb9d718
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07514566B2

Reaction notes

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