Hydrochloric Acid → Pilocarpine

HRID 1461496Notes

Reaction equation

C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][CH2:14][C@H:15]1[C:19](=[O:20])[O:18][CH2:17][C@@H:16]1[CH2:21][C:22]1[N:26]([CH3:27])[CH:25]=[N:24][CH:23]=1.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C.Cl>CCCCCC.O1CCCC1>[CH3:13][CH2:14][C@@H:15]1[C:19](=[O:20])[O:18][CH2:17][C@@H:16]1[CH2:21][C:22]1[N:26]([CH3:27])[CH:25]=[N:24][CH:23]=1

Participants

Conditions

Temperature: -78 °C

Procedure

0.97 ml of a 15% solution of n-butyllithium in hexane is added at 0° C. to a solution of 0.21 ml of diisopropylamine in tetrahydrofuran. After stirring for 15 minutes and cooling to -78° C., 100 mg of (+)-isopilocarpine dissolved in 1 ml of tetrahydrofuran are added, and the mixture is stirred at -78° C. for 10 hours. After the addition of 1 g of 2,6-di-tert.-butyl-4-methylphenol, warming to room temperature and addition of 15 ml of hydrochloric acid (0.5 N), the layers are separated. The aqueous layer is washed twice with 25 ml of chloroform. Concentration of the organic layer and preparative separation on an HPLC column gives optically pure (+)-pilocarpine which is converted into the pilocarpine nitrate, m.p. 174° C., αD =+81° (c=1.618, water) with nitric acid (65%) in ethanol. Reference1 : R. S. Compagnone, H. Rapoport, J. Org. Chem. 51, 1713-1719 (1986)

Workup

additionare added
stirringthe mixture is stirred at -78° C. for 10 hours
temperaturewarming to room temperature
customthe layers are separated
washThe aqueous layer is washed twice with 25 ml of chloroform
customConcentration of the organic layer and preparative separation on an HPLC column

Sources & evidence

ORD record: ord-6a06e6c1fa664926b4924ce17f1cf3e1
Source dataset: uspto-grants-1991_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05075452

Reaction notes

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