Hydrochloric Acid → 4-[3-(2-Ethoxycarbonyl-2-oxo-ethyl)-4-nitro-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 19891Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([CH3:24])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:25]([O:27][C:28](=[O:34])[C:29](OCC)=[O:30])[CH3:26].CC([O-])(C)C.[K+].C(O)C.Cl>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([CH2:24][C:29]([C:28]([O:27][CH2:25][CH3:26])=[O:34])=[O:30])[CH:16]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 2.5 °C

Procedure

A solution of 4-(3-methyl-4-nitro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (example 43, step 1, 41.9 g, 1.0 eq.) and diethyloxalate (18.77 mL, 1.1 eq.) in tetrahydrofuran (241.7 mL) was dropped into a cold (0-5° C.) solution of potassium tert-butylate (28.54 g, 2.0 eq.) and ethanol (43.64 mL, 6.0 eq.) in tetrahydrofuran (1.022 L). The mixture was stirred for 3 h at 0-5° C. and for 18.5 h at room temperature, poured into 1M hydrochloric acid solution. The aqueous phase was extracted 3 times with tert-butylmethylether and the combined organic phases were washed with brine, dried over sodium sulfate, filtered, evaporated to dryness in vacuo and crystallized from ethanol to yield 44.09 g (81%) as white crystals. MS (m/e): 436.2 (M, 5%).

Workup

extractionThe aqueous phase was extracted 3 times with tert-butylmethylether
washthe combined organic phases were washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
customevaporated to dryness in vacuo
customcrystallized from ethanol
customto yield 44.09 g (81%) as white crystals

Sources & evidence

ORD record: ord-b035439c9dd4428fb713f77542cf98c5
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745479B2

Reaction notes

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