Potassium Carbonate → tert-butyl N-(4-cyano-2-fluorobenzyl)-N-methylglycinate

HRID 2410516Notes

Reaction equation

[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Br)=[C:5]([F:11])[CH:4]=1)#[N:2].Cl.[C:13]([O:17][C:18](=[O:22])[CH2:19][NH:20][CH3:21])([CH3:16])([CH3:15])[CH3:14].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7][N:20]([CH3:21])[CH2:19][C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:22])=[C:5]([F:11])[CH:4]=1)#[N:2]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 4-cyano-2-fluorobenzyl bromide (250 g, 1.17 mol), sarcosine tert-butyl ester hydrochloride (212.2 g, 1.17 mol) and potassium carbonate (484 g, 3.50 mol) in acetone (2 L) was stirred 24 hours at 50° C. and 18 hours at RT. The reaction mixture was filtered and the filtrate was concentrated under vacuum. The residue was taken up with water (1 L) and extracted with ethyl acetate (2×1 L). The combined organic layers were washed with water (1 L), dried (MgSO4) and concentrated under vacuum to give the title compound as a yellow-brown oil (325 g, quantitative). 1H NMR (DMSO-d6, 300 MHz) δ 7.82 (dd, J=9.9, 1.4 Hz, 1H), 7.70 (dd, J=7.9, 1.5 Hz, 1H), 7.64 (m, 1H), 3.78 (s, 2H), 3.23 (s, 2H), 2.27 (s, 3H), 1.42 (s, 9H). LC/MS (Method B): 279.2 (M+H)+.

Workup

filtrationThe reaction mixture was filtered
concentrationthe filtrate was concentrated under vacuum
extractionextracted with ethyl acetate (2×1 L)
washThe combined organic layers were washed with water (1 L)
dry with materialdried (MgSO4)
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-8d737b90530b4eb592b88287e00ebeae
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815919B2

Reaction notes

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