Sulfuric Acid → 6-[(4R)-4-Amino-2-oxopyrrolidin-1-yl]-2H-1,4-benzoxazin-3(4H)-one

HRID 1847029Notes

Reaction equation

C(OC(=O)[NH:7][C@@H:8]1[CH2:12][C:11](=[O:13])[N:10]([C:14]2[CH:15]=[CH:16][C:17]3[O:22][CH2:21][C:20](=[O:23])[N:19](COC)[C:18]=3[CH:27]=2)[CH2:9]1)(C)(C)C.[Cl-].[Li+].S(=O)(=O)(O)O.C(=O)([O-])O.[Na+]>CO>[NH2:7][C@H:8]1[CH2:9][N:10]([C:14]2[CH:15]=[CH:16][C:17]3[O:22][CH2:21][C:20](=[O:23])[NH:19][C:18]=3[CH:27]=2)[C:11](=[O:13])[CH2:12]1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of {(3R)-1-[4-(methoxymethyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl]-5-oxopyrrolidin-3-yl}carbamic acid tert-butyl ester (120 mg, 0.31 mmol) in methanol (2 ml) was cooled in an ice bath. Lithium chloride (80 mg, 0.92 mmol) and concentrated sulfuric acid (0.5 ml) were added thereto, and the mixture was then stirred at 80° C. for 2 hours. After cooling, the reaction solution was neutralized with a saturated sodium hydrogen carbonate aqueous solution and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, chloroform/methanol) to yield 58 mg (75%) of the title compound in the form of a colorless solid.

Workup

temperatureAfter cooling
concentrationthe solvent was concentrated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography (NH silica gel, chloroform/methanol)

Sources & evidence

ORD record: ord-bb1c8fe9eeeb4d04b5e5ba68a930521b
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952010B2

Reaction notes

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