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

HRID 1157653Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([Mg]Br)[CH:6]=[CH:7][CH:8]=1.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C:19]1=[O:23])=[O:17])([CH3:14])([CH3:13])[CH3:12]>O1CCCC1>[C:11]([O:15][C:16](=[O:17])[NH:18][CH2:22][CH2:21][CH2:20][C:19]([C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)=[O:23])([CH3:14])([CH3:12])[CH3:13]

Participants

Conditions

Temperature: -40 °C

Procedure

Add 3-methoxyphenylmagnesium bromide (1.0 M in tetrahydrofuran, 91.0 mL, 91.0 mmol) dropwise to 1-(tert-butoxycarbonyl)-2-pyrrolidinone (11.9 mL, 70.0 mmol) in tetrahydrofuran (230 mL) at −40° C. After stirring at −40° C. for one hour, warm to 0° C. for 2 h before quenching with 2 M hydrochloric acid (70 mL). Dilute with methylene chloride (250 mL), separate the layers, and extract the aqueous layer with methylene chloride (2×200 mL). Dry the combined organic layers over magnesium sulfate, filter, and concentrate under reduced pressure to obtain the title compound (23.20 g, >100%). MS (APCI+): 194 [C16H23NO4—C5H8O2+H]+; 1H NMR (300 MHz, CDCl3): δ 7.55-7.47 (m, 2H), 7.39-7.33 (m, 1H), 7.12-7.08 (m, 1H), 4.66 (bs, 1H), 3.85 (s, 3H), 3.29-3.18 (m, 2H), 3.01 (t, J=7.1 Hz, 2H), 1.93 (quintet, J=7.0 Hz, 2H), 1.42 (s, 9H).

Workup

temperaturewarm to 0° C. for 2 h
custombefore quenching with 2 M hydrochloric acid (70 mL)
additionDilute with methylene chloride (250 mL)
customseparate the layers
extractionextract the aqueous layer with methylene chloride (2×200 mL)
dry with materialDry the combined organic layers over magnesium sulfate
filtrationfilter
concentrationconcentrate under reduced pressure

Sources & evidence

ORD record: ord-5b038a462cc748b586c739962d84ee9e
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07807691B2

Reaction notes

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