Imidazole → (2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-N-(2-oxo-2-phenylethyl)butanamide

HRID 470795Notes

Reaction equation

HRID 470795 reaction equation
[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([NH:10][C@H:11]([C@@H:24]([OH:26])[CH3:25])[C:12]([NH:14][CH2:15][C:16](=[O:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].CN(C=O)C.N1C=CN=C1.[C:38]([Si:42](Cl)([CH3:44])[CH3:43])([CH3:41])([CH3:40])[CH3:39]>CCOC(C)=O.O>[Si:42]([O:26][C@@H:24]([CH3:25])[C@@H:11]([NH:10][C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=1[CH3:27])[C:12]([NH:14][CH2:15][C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:13])([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:44])[CH3:43]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 57908663(2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxy-N-(2-oxo-2-phenylethyl)butanamide

Product 1

HCID 57908587(2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-N-(2-oxo-2-phenylethyl)butanamideYield 80.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A 500 mL round bottomed flask was charged with (2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-N-(2-oxo-2-phenylethyl)butanamide (7.87 g, 20.4 mmol) and DMF (200 mL) then cooled to 0° C. Imidazole (6.94 g, 102 mmol) and tert-butylchlorodimethylsilane (9.22 g, 61.2 mmol) were added and the mixture was stirred and warmed to room temperature overnight. Water (200 mL) was added to the mixture followed by EtOAc (200 mL) and the phases partitioned. The organic phase was washed with water (2×100 mL), brine (100 mL), dried (Na2SO4) and concentrated to furnish the title compound as a white solid (8.2 g, 80%). 1H NMR (500 MHz, acetone-d6, δ in ppm) 7.97 (d, J=8 Hz, 2H), 7.44-7.66 (m, 1H), 0.40 (d, J=8 Hz, 1H), 6.42 (d, J=8 Hz, 1H), 5.43 (d, J=6 Hz, 1H), 4.77 (dd, J=6, 8 Hz, 2H), 4.79 (dd, J=5, 15 Hz, 2H), 4.70 (d, J=5, 15 Hz, 1H), 4.52-4.58 (m, 1H), 3.85-4.89 (m, 1H), 2.39 (s, 3H), 1.24 (d, J=6 Hz, 3H).

Workup

  1. temperaturewarmed to room temperature overnight
  2. customthe phases partitioned
  3. washThe organic phase was washed with water (2×100 mL), brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8e7edea6f1684785aa506bd0a742448e
Source dataset
uspto-grants-2014_01
Patent number
US08629167B2

Reaction notes

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