Lithium hydroxide, monohydrate → 1-(tert-butoxycarbonyl)-4-(hydroxymethyl)piperidine-4-carboxylic acid

HRID 1584384Notes

Reaction equation

O.[OH-].[Li+].C([O:6][C:7]([C:9]1([CH2:22][OH:23])[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)=[O:8])C>CO.O>[C:18]([O:17][C:15]([N:12]1[CH2:13][CH2:14][C:9]([CH2:22][OH:23])([C:7]([OH:8])=[O:6])[CH2:10][CH2:11]1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

Conditions

Temperature: 0 °C

Procedure

Lithium hydroxide monohydrate (6.95 g, 165.6 mmol) was added to solution of N-(tert-butoxycarbonyl)-4-(hydroxymethyl)piperidine-4-carboxylic acid ethyl ester (9.52 g, 33.1 mmol) in 2:1 methanol/water (100 mL). The mixture was heated to reflux for 30 minutes, the methanol removed in vacuo by concentration using a bath temperature no higher than 45° C. The aqueous layer was cooled to 0° C., acidified to pH 3.0 using 6M aqueous hydrochloric acid, and extracted with ethyl acetate (4×75 mL). The combined organic layers were dried over magnesium sultate, and concentrated in vacuo, and recrystallized from dichloromethane/hexanes to afford N-(tert-butoxycarbonyl)-4-(hydroxymethyl)piperidine-4-carboxylic acid (8.59 g, 100%).

Workup

temperatureThe mixture was heated
temperatureto reflux for 30 minutes
customthe methanol removed in vacuo by concentration
customno higher than 45° C
extractionextracted with ethyl acetate (4×75 mL)
dry with materialThe combined organic layers were dried over magnesium sultate
concentrationconcentrated in vacuo
customrecrystallized from dichloromethane/hexanes

Sources & evidence

ORD record: ord-da8d18a3117c4f64a16cc10567072c7e
Source dataset: uspto-grants-1999_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05932595

Reaction notes

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