Oxalyl chloride → HCID 86639356, compound

HRID 1624181Notes

Reaction equation

HRID 1624181 reaction equation
[CH3:1][O:2][C:3](/[CH:5]=[CH:6]/[C:7]([O:9][CH:10]([CH3:14])C(O)=O)=[O:8])=[O:4].C(Cl)(=O)[C:16](Cl)=[O:17].[CH2:21]([O:23][C:24](=[O:34])[CH2:25][NH:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:22].C(N(C(C)C)CC)(C)C>ClCCl.CN(C1C=CN=CC=1)C.CN(C)C=O>[C:7]([O:9][CH2:10][CH2:14][C:16](=[O:17])[N:26]([CH2:25][C:24]([O:23][CH2:21][CH3:22])=[O:34])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)(=[O:8])/[CH:6]=[CH:5]/[C:3]([O:2][CH3:1])=[O:4]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 80908N-Benzylglycine ethyl esterHCID 81531DiisopropylethylamineHCID 86639357HCID 86639357, compound

Product 1

HCID 86639356HCID 86639356, compoundYield 33.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

Following general procedure B2, 2-[(2E)-3-(methoxycarbonyl)prop-2-enoyloxy]propanoic acid (24) (0.50 g, 2.47 mmol) was activated with oxalyl chloride (0.25 mL, 0.35 g, 2.71 mmol) in dichloromethane (DCM) at ca. 0° C. and in the presence of a catalytic amount of N,N-dimethylformamide (DMF). A DCM solution of the freshly prepared crude acid chloride was reacted ca. 0° C. (ice bath) with N-benzyl glycine ethyl ester (Bn-Gly-OEt) (0.56 g, 2.90 mmol) in DCM and diisopropylethylamine (DIEA) (0.506 mL, 0.376 g, 2.90 mmol) in the presence of a catalytic amount of 4-(N,N-dimethyl)aminopyridine (DMAP). After aqueous work-up and isolation, and purification by silica gel flash chromatography afforded 0.31 g (33% yield) of the title compound (37) as a white solid. 1H NMR (CDCl3, 400 MHz, all rotamers): δ 7.37-7.17 (m, 5H), 6.88-6.77 (m, 2H), 5.49 (q, J=6.4 Hz, 0.75H), 5.33 (q, J=6.4 Hz, 0.25H), 4.7-4.27 (m, 3H), 4.16-4.13 (m, 2H), 3.83-3.63 (m, 4H), 1.53 (d, J=6.8 Hz, 3H), 1.21 (t, J=4.0 Hz, 3H). MS (ESI): m/z 378.10 (M+H)+.

Workup

  1. customAfter aqueous work-up and isolation, and purification by silica gel flash chromatography

Sources & evidence

ORD record
ord-088bc6b85ece473f9b51bb4874c10b55
Source dataset
uspto-grants-2014_07
Patent number
US08778991B2

Reaction notes

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