Methanesulfonic Acid → 1-(1-(3-Isothiocyanatophenyl)cyclohexyl)piperidine

HRID 34593Notes

Reaction equation

HRID 34593 reaction equation
[CH3:1][S:2]([O-])(=O)=O.[CH2:6]1[CH2:11][CH2:10][C:9]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([NH2:18])[CH:13]=2)[CH2:8][CH2:7]1.C(=O)(O)[O-].[Na+].C(Cl)(Cl)=S.CS(O)(=O)=O>C(Cl)(Cl)Cl.O.O1CCCC1>[CH2:6]1[CH2:11][CH2:10][C:9]([N:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]2)([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N:18]=[C:1]=[S:2])[CH:13]=2)[CH2:8][CH2:7]1

Participants

9

Reactant 5

HCID 6395Methanesulfonic AcidHCID 10040ThiophosgeneHCID 85257MethanesulfonateHCID 516892Sodium BicarbonateHCID 100381543-Aminophencyclidine

Product 1

HCID 1147451-(1-(3-Isothiocyanatophenyl)cyclohexyl)piperidine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Metaphit was prepared as methanesulfonate and hydrochloride salts. To a vigorously stirred two-phase system consisting of 4.65 g (18 mmol) of m-amino-PCP (1-(1-(3-aminophenyl)cyclohexyl)piperidine) in 50 ml of chloroform and 756 mg (90 mmol) of sodium bicarbonate in 25 ml water, was added a solution of 1.45 ml (2.29 g, 19 mmol) of freshly distilled thiophosgene in 10 ml of chloroform. The mixture was stirred for 5 minutes, then the phases were separated and the aqueous phase was washed once with chloroform. The combined organic layers were dried (over sodium sulfate) and evaporated to a clear glass (5.43 g). This substance was dissolved in tetrahydrofuran (20 ml) and treated with a solution of methanesulfonic acid (1.73 g, 18 mmol) in tetrahydrofuran. The resulting crystalline solid was filtered and dried in vacuo to give 7.01 g (98%) of methanesulfonate salt, mp 175°-178° C. (dec). The material could be recrystallized from isopropanol/isopropyl ether if necessary. It was stored at 0° C. in a dessicator. The hydrochloride salt prepared in isopropanol and recrystallized from methanol-ether showed mp 214°-216 ° C. The methanesulfonate salt was considerably more soluble in water than the hydrochloride.

Workup

  1. customthe phases were separated
  2. washthe aqueous phase was washed once with chloroform
  3. dry with materialThe combined organic layers were dried (over sodium sulfate)
  4. customevaporated to a clear glass (5.43 g)
  5. dissolutionThis substance was dissolved in tetrahydrofuran (20 ml)
  6. filtrationThe resulting crystalline solid was filtered
  7. customdried in vacuo

Sources & evidence

ORD record
ord-5bbd7a0eed7e4d939276433b5fb045d4
Source dataset
uspto-grants-1988_08
Patent number
US04762846

Reaction notes

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