Hydrochloric Acid → 1-[1-(3-Chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol Dihydrochloride

HRID 902246Notes

Reaction equation

HRID 902246 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([C:16]2([OH:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:9][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:5]=[CH:6][CH:7]=1.[ClH:23].C(OCC)C>CO>[ClH:1].[ClH:23].[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([C:16]2([OH:22])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)[CH2:9][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 103815021-[1-(3-Chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol

Product 1

HCID 113838871-[1-(3-Chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol DihydrochlorideYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 4-[(3-chlorophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate (200 mg, 0.46 mmol) in dry tetrahydrofuran (3 mL) under nitrogen was treated dropwise with a solution of borane (1.0 M in tetrahydrofuran, 1.60 mL, 1.60 mmol). The resulting solution was heated at 70° C. for 2 h, after which time the reaction was cooled in an ice bath and was treated dropwise with a 2N aqueous solution of hydrochloric acid (1 mL). The reaction was again heated at 70° C. for 1 h, and was then cooled and treated with methanol (1 mL). After the solvent was removed in vacuo, the resulting residue was dissolved in water (5 mL) and was washed with ethyl acetate (1×4 mL). The aqueous layer was basified with the addition of a 2 N aqueous solution of sodium hydroxide until the pH=10. The product was extracted with ethyl acetate (4×5 mL) and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo to yield 146 mg (99%) 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol as a colorless oil. HRMS: calcd for C18H27ClN2O, 322.1812; found (ESI_FT), 323.18977. 1-[1-(3-Chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol (146 mg) was dissolved in methanol (0.5 mL) and treated with a saturated methanolic solution of hydrochloric acid (0.5 mL) followed by diethyl ether. After crystallizing in the refrigerator for 16 h, the resulting solid was collected, washed with diethyl ether and dried in vacuo to yield 110 mg (60%) 1-[1-(3-chlorophenyl)-2-piperazin-1-ylethyl]cyclohexanol dihydrochloride as a white solid. MS (ESI) m/z 323/325 ([M+H]+); HRMS: calcd for C18H27ClN2O.2.00 HCl, 394.1345; found (ESI_FT), 323.18831.

Workup

  1. customAfter crystallizing in the refrigerator for 16 h
  2. customthe resulting solid was collected
  3. washwashed with diethyl ether
  4. customdried in vacuo

Sources & evidence

ORD record
ord-e926529920a14e68a5ccd964f5acb539
Source dataset
uspto-grants-2008_04
Patent number
US07365076B2

Reaction notes

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