Lithium borohydride → 4-{5-Chloro-2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile

HRID 1436436Notes

Reaction equation

[Cl:1][C:2]1[S:6][C:5]([NH:7][C:8]([CH3:12])([CH3:11])[CH:9]=[O:10])=[N:4][C:3]=1[C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][CH:14]=1.[BH4-].[Li+]>O1CCCC1>[Cl:1][C:2]1[S:6][C:5]([NH:7][C:8]([CH3:12])([CH3:11])[CH2:9][OH:10])=[N:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]([C:17]#[N:18])=[CH:19][CH:20]=1

Participants

Conditions

Temperature: 0 °C

Procedure

4-{5-Chloro-2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile (1.15 g, 3.76 mmol), prepared in the previous step, was dissolved in tetrahydrofuran (20 mL) and cooled to 0° C. Lithium borohydride (2M in tetrahydrofuran; 2.25 mL, 2.5 mmol) was added dropwise and the mixture was stirred for 1 h. The reaction was quenched with saturated NH4Cl, diluted with ethyl acetate and washed with H2O, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (20% acetone/hexane) afforded 4-{5-chloro-2-[(2-hydroxy-1,1-dimethylethyl)amino]-1,3-thiazol-4-yl}benzonitrile (1.01 g, 88%) as a white solid. HRMS: calcd for C14H14ClN3OS+H+, 308.06188; found (ESI, [M+H]+), 308.0612; Analytical HPLC: purity 100% at 210-370 nm, 10.0 min; 100% at 252 nm, 10.0 min; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.

Workup

customThe reaction was quenched with saturated NH4Cl
additiondiluted with ethyl acetate
washwashed with H2O, brine
dry with materialdried over anhydrous MgSO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-21cd53d442e24571869a350cc96a0a1a
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618990B2

Reaction notes

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