Imidazole → tert-butyl N-[2-{[tert-butyl(dimethyl)silyl]oxy}-1-(4-cyanophenyl)ethyl]-D-alaninate

HRID 572585Notes

Reaction equation

HRID 572585 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([NH:12][C@@H:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH3:14])[CH2:10][OH:11])=[CH:5][CH:4]=1)#[N:2].N1C=CN=C1.[Si:27](Cl)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].O>C(Cl)Cl>[Si:27]([O:11][CH2:10][CH:9]([NH:12][C@@H:13]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH3:14])[C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 66653013tert-butyl N-[1-(4-cyanophenyl)-2-hydroxyethyl]-D-alaninate

Product 1

HCID 66652924tert-butyl N-[2-{[tert-butyl(dimethyl)silyl]oxy}-1-(4-cyanophenyl)ethyl]-D-alaninateYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl N-[1-(4-cyanophenyl)-2-hydroxyethyl]-D-alaninate (2 g, 0.0068 mol) in DCM (30 ml) were added imidazole (0.92 g, 0.0136 mol) and tert-Butyldimethylsilylchloride (1.25 g, 0.0082 mol) at RT. The reaction mixture was stirred at RT for 6 h and portioned between DCM and water, separated the layer and concentrated under reduced pressure. The crude material was purified by column chromatography using petroleum ether and ethyl acetate (80:20) as an eluent to afford (2 g, 74%) of the title compound as brown oil. 1H NMR: (DMSO-d6, 400 MHz) δ 7.80-7.77 (m, 2H), 7.53-7.50 (m, 2H), 4.86-4.85 (t, J=3.9 Hz, 1H), 3.17-3.13 (m, 1H), 2.61-2.55 (m, 1H), 1.95-1.89 (m, 1H), 1.39 (s, 9H), 1.09-1.07 (d, J=7.1 Hz, 3H), 0.80 (s, 9H), 0.04 (s, 3H), −0.12 (s, 3H). LC/MS (Method A): 405.3 (M+H)+. HPLC (Method A) Rt 5.13 min. (Purity: 73.7%).

Workup

  1. customseparated the layer
  2. concentrationconcentrated under reduced pressure
  3. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-fc87e670ac6d460496d766f3396114b6
Source dataset
uspto-grants-2015_05
Patent number
US09029405B2

Reaction notes

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