Borane → Tert-butyl{1-[2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate

HRID 749662Notes

Reaction equation

HRID 749662 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([C:26]2([OH:32])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[C:10]([N:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19](=[O:25])[O:20]CCCC)[CH2:14][CH2:13]2)=O)[CH:5]=[CH:6][C:7]=1[Cl:8].B>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([C:26]2([OH:32])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:10][N:12]2[CH2:17][CH2:16][CH:15]([NH:18][C:19](=[O:25])[O:20][C:4]([CH3:9])([CH3:5])[CH3:3])[CH2:14][CH2:13]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 6331BoraneHCID 86601090HCID 86601090, compound

Product 1

HCID 86599032Tert-butyl{1-[2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamateYield 105.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
74 °C

Procedure

A solution of tent-butyl {1-[(3,4-dichlorophenyl)(1-hydroxycyclohexyl)acetyl]piperidin-4-yl}carbamate (364 mg, 0.75 mmol) in dry tetrahydrofuran (1 mL), under nitrogen, was treated with a solution of borane (1.0 M in tetrahydrofuran, 2.62 mL, 2.62 mmol). The reaction was heated at 74° C. for 2 h, after which time the reaction was cooled and quenched by the addition of methanol (4 mL). The solvents were removed in vacuo, and the products were purified via Biotage Horizon (FLASH 25 M, silica, gradient from 10% EtOAc/hexane to 90% EtOAc/hexane) to yield 187 mg (53%) tert-butyl {1-[2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate as a white foam which eluted first and 88 mg (31%) 1-{1-(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol as a colorless oil which eluted second. tert-butyl {1-[2-(3,4-dichlorophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperidin-4-yl}carbamate: MS (ES) m/z 471.3 ([M+H]+); HRMS: calcd for C24H36Cl2N2O3, 470.2103; found (ESI), 471.2165. 1-{1-(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol: MS m/z 385/387/389 ([M+H]+). 1-{1-(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol was converted to the dihydrochloride salt with a methanolic solution of hydrochloric acid and diethyl ether to yield 45 mg (41%) 1-{1-(3,4-dichlorophenyl)-2-[4-(methylamino)piperidin-1-yl]ethyl}cyclohexanol dihydrochloride as a white solid. HRMS: calcd for C20H30Cl2N2O.2.00 HCl, 456.1269; found (ESI), 385.183.

Workup

  1. temperatureafter which time the reaction was cooled
  2. customquenched by the addition of methanol (4 mL)
  3. customThe solvents were removed in vacuo
  4. customthe products were purified via Biotage Horizon (FLASH 25 M, silica, gradient from 10% EtOAc/hexane to 90% EtOAc/hexane)

Sources & evidence

ORD record
ord-af9a143d22044075b02077bb8fdb610f
Source dataset
uspto-grants-2008_07
Patent number
US07402698B2

Reaction notes

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