Methyl chloroformate → N-(methoxycarbonyl)-L-valyl-L-proline tert-butyl ester

HRID 2293802Notes

Reaction equation

C(=O)([O-])[O-].[Na+].[Na+].Cl[C:8]([O:10][CH3:11])=[O:9].[C:12]([O:16][C:17](=[O:30])[C@@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[C:23](=[O:29])[C@H:24]([CH:26]([CH3:28])[CH3:27])[NH2:25])([CH3:15])([CH3:14])[CH3:13]>O.O1CCCC1.CCOCC>[C:12]([O:16][C:17](=[O:30])[C@@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[C:23](=[O:29])[C@H:24]([CH:26]([CH3:27])[CH3:28])[NH:25][C:8]([O:10][CH3:11])=[O:9])([CH3:14])([CH3:13])[CH3:15]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of sodium carbonate (110.5 g) in water (1.5 litres) and L-Valyl-L-Proline tert-butyl ester in tetrahydrofuran (THF; 1 litre) were combined and cooled to 0° C. The mixture was diluted with ether (400 ml) and methyl chloroformate (39.4 g) was added dropwise. The reaction mixture was then allowed to warm ambient temperature over 2 hours. The layers were separated and the organic phase was washed twice with 1M hydrochloric acid, followed by saturated aqueous sodium bicarbonate solution and brine. The aqueous phase was extracted with ether. All organic phases were combined and dried (MgSO4) and the solvent removed to give N-(methoxycarbonyl)-L-valyl-L-proline tert-butyl ester (125.9 g); 1H NMR (300 MHz, DHSO/d4-trifluoroacetic acid): 4.23 (dd, 1H), 4.06 (d, 1H), 3.78 (m, 1H), 3.57 (m, 1H), 3.55 (s, 3H), 2.16 (m, 1H), 1.95 (m, 3H), 1.80 (m, 1H), 1.42 (s, 9H), 0.94 (m, 6H); MS: m/z=329 (H+1).

Workup

additionwas added dropwise
temperatureto warm ambient temperature over 2 hours
customThe layers were separated
washthe organic phase was washed twice with 1M hydrochloric acid
extractionThe aqueous phase was extracted with ether
dry with materialdried (MgSO4)
customthe solvent removed

Sources & evidence

ORD record: ord-2e2db1cacdb143a6ae6bfb2ac4cfb6ad
Source dataset: uspto-grants-1997_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05686628

Reaction notes

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