Hydrochloric Acid → trans-1-Tert-butoxycarbonyl-4-methyl-piperidine-3-carboxylic acid

HRID 1808707Notes

Reaction equation

C([O:3][C:4]([CH:6]1[CH:11]([CH3:12])[CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7]1)=[O:5])C.CO.[OH-].[Li+].Cl>O1CCCC1>[C:16]([O:15][C:13]([N:8]1[CH2:9][CH2:10][C@@H:11]([CH3:12])[C@H:6]([C:4]([OH:5])=[O:3])[CH2:7]1)=[O:14])([CH3:17])([CH3:18])[CH3:19]

Participants

Conditions

Temperature: 60 °C

Procedure

To a flask containing (+/−)-4-methyl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (1.12 g, 4.1 mmol; from example 8 above) was taken up in tetrahydrofuran (12 mL) and methanol (3 mL) and cooled to 0° C. (ice bath). A solution of lithium hydroxide (4.5 mL, 1M) was added and the mixture was warmed to ambient over 3 hours. Extra methanol (2 mL) was added and the material was heated to 60° C. (oil bath) for 5.5 hours. The mixture was cooled to ambient and treated with 1N hydrochloric acid solution (4.7 mL) with vigorous stirring. The solvent was stripped and the remainder was dried under high vacuum for several hours, providing 1.06 g of mainly trans-(+/−)-4-methyl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester: as a off-white solid. MS (M−H)−=242.

Workup

temperaturethe mixture was warmed
temperatureThe mixture was cooled to ambient and
customthe remainder was dried under high vacuum for several hours

Sources & evidence

ORD record: ord-f99dfc6952de45fd920a9ba89c447e36
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08361962B2

Reaction notes

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