Hydrochloric Acid → 1-((Benzyloxy)carbonyl)piperidine-3-carboxylic acid

HRID 659602Notes

Reaction equation

[OH-].[Na+].[NH:3]1[CH2:8][CH2:7][CH2:6][CH:5]([C:9]([OH:11])=[O:10])[CH2:4]1.[C:12](Cl)(=[O:21])[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl>O.CCOCC.CCOC(C)=O>[CH2:14]([O:13][C:12]([N:3]1[CH2:8][CH2:7][CH2:6][CH:5]([C:9]([OH:11])=[O:10])[CH2:4]1)=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 5 °C

Procedure

A 500-mL 4-necked round-bottom flask was charged with a solution of NaOH (8 g, 198.00 mmol, 1.00 equiv, 99%) in H2O (200 mL). To this was added piperidine-3-carboxylic acid (25.8 g, 197.75 mmol, 1.00 equiv, 99%), in small portions at 0° C. Then, a solution of benzyl carbonochloridate (39.2 g, 227.48 mmol, 1.15 equiv, 99%) in Et2O (50 mL) was added at 0° C. over 40 minutes. Then a solution of NaOH (12 g, 1.50 equiv) in H2O (300 mL) was added drop wise with stirring at 0-10° C. The resulting solution was allowed to stir overnight at room temperature. The reaction progress was monitored by TLC (EtOAc/PE=1/1). The pH adjusted to 3 with 10% aqueous HCl. The resulting solution was extracted with ethyl acetate (3×500 mL). Combined organic layers were dried over anhydrous magnesium sulfate and concentrated on a rotary evaporator to afford 1-(benzyloxycarbonyl)piperidine-3-carboxylic acid (58 g) as white solid.

Workup

customat 0° C
stirringto stir overnight at room temperature
extractionThe resulting solution was extracted with ethyl acetate (3×500 mL)
dry with materialCombined organic layers were dried over anhydrous magnesium sulfate
concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record: ord-165347d5b43d4b3e9dec72931b149ea0
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08080566B1

Reaction notes

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