Dimethylformamide → HCID 131729540, compound

HRID 1626065Notes

Reaction equation

HRID 1626065 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(Cl)=O.[CH2:21]([O:23][C:24](=[O:28])CNC)[CH3:22].C(N(C(C)C)CC)(C)C.[CH3:38][N:39]([CH3:42])[CH:40]=[O:41]>ClCCl.CN(C1C=CN=CC=1)C>[C:7]([O:9][CH2:10][CH2:14][C:40](=[O:41])[N:39]([CH2:42][C:24]([O:23][CH2:21][CH3:22])=[O:28])[CH3:38])(=[O:8])/[CH:6]=[CH:5]/[C:3]([O:2][CH3:1])=[O:4]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 95849Glycine, N-methyl-, ethyl esterHCID 86639357HCID 86639357, compound

Product 1

HCID 131729540HCID 131729540, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 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 sarcosine ethyl ester (H-Sar-OEt) (0.43 g, 2.90 mmol) and diisopropylethylamine (DIEA) (0.506 mL, 0.376 g, 2.90 mmol) in DCM and 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 0.30 g (39% yield) of the title compound (38) as a white solid. 1H NMR (CDCl3, 400 MHz, all rotamers): δ 6.88-6.81 (m, 2H), 5.47 (q, 0.75H, J=6.8 Hz), 5.32 (q, 0.25H, J=6.8 Hz), 4.40-4.33 (m, 1H), 4.16-4.11 (m, 2H), 3.94-3.75 (m, 4H), 3.10 (s, 2.25H), 2.96 (s, 0.75H), 1.50-1.44 (dd, 3H), 1.26-1.20 (m, 3H). MS (ESI): m/z 302.09 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-00fb02452265492190360699a2f2ae9b
Source dataset
uspto-grants-2014_07
Patent number
US08785443B2

Reaction notes

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