1-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl ester → tert-butyl N-[4-(3-fluorophenyl)-4-oxobutyl]carbamate

HRID 63992

Reaction equation

[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[F:14][C:15]1[CH:16]=[C:17]([Mg]Br)[CH:18]=[CH:19][CH:20]=1>C1COCC1>[F:14][C:15]1[CH:20]=[C:19]([C:2](=[O:1])[CH2:6][CH2:5][CH2:4][NH:3][C:7](=[O:8])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH:18]=[CH:17][CH:16]=1

Participants

Conditions

Temperature: -78 °C

Procedure

In a round-bottomed flask was charged tert-butyl 2-oxopyrrolidine-1-carboxylate (2.2 g, 11.9 mmol) and THF (25 mL). The mixture was cooled down to −78° C. first, followed by slow addition of (3-fluorophenyl)magnesium bromide (17.8 mL, 17.8 mmol, 1.0 M solution in THF) over 15 minutes. The mixture was stirred for 3 hours, during which time the bath temperature rose from −78° C. to −10° C. The reaction was quenched by drop-wise addition of 1N HCl (2 mL) and warmed up to ambient temperature, followed by addition of EtOAc and water. After separating the organic layer, the aqueous layer was extracted with EtOAc three times. The combined organic layers was dried over Na2SO4 and concentrated to yield the product as a clear oil.

Workup

customrose from −78° C. to −10° C
customThe reaction was quenched by drop-wise addition of 1N HCl (2 mL)
temperaturewarmed up to ambient temperature
additionfollowed by addition of EtOAc and water
customAfter separating the organic layer
extractionthe aqueous layer was extracted with EtOAc three times
dry with materialThe combined organic layers was dried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-0e0d6802bbec4410b6ba92c729e66ce8
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09447104B2

Linked notes

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