1-(1,1-Dimethylethyl) 2-ethyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylate → (S)-2-tert-Butoxycarbonylamino-5-oxo-hexanoic acid ethyl ester

HRID 1504325Notes

Reaction equation

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

Participants

Conditions

Temperature: -43 °C

Procedure

A solution of (S)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (20 g, 10 mmol) in dry THF (150 mL) was cooled to −50° C., and then methylmagnesium bromide (31 mL, 93.28 mmol) was added dropwise at a temperature between −50 and −44° C. in 30 min. The reaction mixture was stirred at −43° C. for 2 h and placed in a freezer (ca. −20° C.) overnight. The mixture was quenched with sat. NH4Cl solution and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product, which was purified by column chromatography (8:1-3:1 petroleum ether:EtOAc) to give the title intermediate (38 g) as light yellow oil. 1H NMR (400 MHz, CDCl3): δ(ppm) 5.11-5.09 (m, 1H), 4.25-4.24 (m, 1H), 4.19 (q, J=7.2 Hz, 2H), 2.63-2.52 (m, 2H), 2.15 (s, 3H), 2.12-2.08 (m, 1H), 1.92-1.82 (m, 1H), 1.44 (s, 9H), 1.28 (t, J=7.2 Hz, 3H).

Workup

customplaced in a freezer (ca. −20° C.) overnight
customThe mixture was quenched with sat. NH4Cl solution
extractionextracted with EtOAc
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customto give the crude product, which
customwas purified by column chromatography (8:1-3:1 petroleum ether:EtOAc)

Sources & evidence

ORD record: ord-9b127c8b82c6494b94f6b8c7a3049a10
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212168B2

Reaction notes

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