Triethylamine → tert-butyl N-[1-(4-cyanophenyl)-2-hydroxyethyl]-D-alaninate

HRID 572584Notes

Reaction equation

[OH:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[CH:7][CH:6]=1)=O.Cl.[C:14]([O:18][C:19](=[O:23])[C@@H:20]([CH3:22])[NH2:21])([CH3:17])([CH3:16])[CH3:15].C(N(CC)CC)C.[BH4-].[Na+]>CO.C(Cl)Cl>[C:11]([C:8]1[CH:9]=[CH:10][C:5]([CH:3]([NH:21][C@@H:20]([C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:23])[CH3:22])[CH2:2][OH:1])=[CH:6][CH:7]=1)#[N:12]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 2-Hydroxy-1-(4-cyanophenyl)ethanone (3.2 g, 0.0198 mol) in methanol and DCM (1:1) (100 ml) were added D-Alanine t-butyl ester hydrochloride (3.6 g, 0.0198 mol) and triethylamine (6.9 ml, 0.0495 mol) at RT. The reaction mixture was heated at 70° C. for 18 h. The reaction mixture was cooled to 0° C. and NaBH4 (0.9 g, 0.0237 mol) was added in portions and stirred at RT for 1 h. The reaction mixture was quenched with ice, extracted with DCM (2×100 ml), dried over sodium sulphate and evaporated. The crude material was purified by column chromatography using chloroform and methanol (90:10) as an eluent to afford (2.5 g, 43%) of title compound as brown oil. 1H NMR: (CD3OD, 400 MHz) δ 7.71-7.69 (d, J=8.36 Hz, 2H), 7.59-7.56 (d, J=8.08 Hz, 2H), 4.76-4.74 (t, J=6.32 Hz, 1H), 3.64-3.61 (q, 2H), 3.44-3.42 (d, J=7.04 Hz, 1H), 1.47 (s, 9H), 1.30-1.28 (d, J=7.04 Hz, 3H). LC/MS (Method A): 291.3 (M+H)+. HPLC (Method A) Rt 2.95 min. (Purity: 76.8%).

Workup

temperatureThe reaction mixture was cooled to 0° C.
customThe reaction mixture was quenched with ice
extractionextracted with DCM (2×100 ml)
dry with materialdried over sodium sulphate
customevaporated
customThe crude material was purified by column chromatography

Sources & evidence

ORD record: ord-a9db460d5c7e4c93a68c618f88ad5372
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029405B2

Reaction notes

Loading…