Benzyl chloroformate → 4-(1-((Benzyloxy)carbonyl)piperidin-4-YL)butanoic acid

HRID 568113Notes

Reaction equation

Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])[CH2:4][CH2:3]1.[CH2:14]([O:21][C:22](Cl)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O.[OH-].[Na+]>[C:15]1([CH2:14][O:21][C:22]([N:2]2[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])[CH2:4][CH2:3]2)=[O:23])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

Conditions

Temperature: 5 °C

Procedure

Either solid 4-(4-piperidyl) butyric acid hydrochloride (124 kg) is dissolved in water (600 kg), or the 16% aqueous solution of 4-(4-piperidyl)butyric acid hydrochloride prepared in step 3 (777 kg), is diluted with aqueous sodium hydroxide (289 kg) in a 1600 liter glass lined reactor cooled at 5° C. Benzylchloroformate (112 kg) is added over a period of 2-3 hours and the solution is heated to about 25° C. The reaction mixture is extracted with methyl tert-butyl ether (476 kg). The aqueous layer is then acidified with hydrochloric acid (187 kg) and extracted with toluene (450 kg). The organic layer is washed with water (240 kg) and dried by azeotropic distillation at atmospheric pressure under nitrogen. The resulting solution of 1-[(phenylmethoxy)carbonyl]-4-piperidinebutanoic acid in toluene is used as is in step 5. Weight of the product in solution: 179 kg. Quality: about 35% w/w in toluene.

Workup

temperaturethe solution is heated to about 25° C
extractionThe reaction mixture is extracted with methyl tert-butyl ether (476 kg)
extractionextracted with toluene (450 kg)
washThe organic layer is washed with water (240 kg)
customdried by azeotropic distillation at atmospheric pressure under nitrogen

Sources & evidence

ORD record: ord-8c2efc96856044189b71dffc418c35ba
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06180759B2

Reaction notes

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