Hydrochloric Acid → HCID 178516031, compound

HRID 1884516Notes

Reaction equation

HRID 1884516 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[C:11]1([CH:17]2[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[BH4-].[Na+].Cl>CC(O)C.C1COCC1>[C:11]1([C@H:17]2[CH2:22][CH2:21][C@H:20]([NH:1][CH2:2][CH2:3][C:4]3[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=3)[CH2:19][CH2:18]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5610TyramineHCID 786054-PhenylcyclohexanoneHCID 4311764Sodium borohydride

Product 1

HCID 178516031HCID 178516031, compoundYield 15.1%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tyramine (3.0 g, 22 mmol) in 2-propanol (100 mL) and THF (50 mL) was added 4-phenylcyclohexanone 1 (3.8 g, 22 mmol) and 3 Å molecular sieves. After 2 hours, sodium borohydride (1.2 g, 31 mmol) was added, and the reaction mixture was stirred overnight. The reaction mixture was quenched with MeOH, filtered through Celite, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (silica, 9:1 CH2Cl2:MeOH) gave the free base which was converted to an HCl salt. Recrystallization from MeOH/Et2O gave the trans-isomer trans-4-[2-(4-phenylcyclohexylamino)ethyl]phenol (0.98 g, 14%): mp 238-241° C.; IR (KBr): 2940, 1517, cm−1; 1H NMR (500 MHz, DMSO-d6) δ 9.30 (s, 1H), 8.99 (br d, 1H), 7.30-7.15 (m, 5H), 7.07 (d, J=8 Hz, 2H), 6.73 (d, J=8 Hz, 2H), 3.10-3.07 (m, 3H), 2.89-2.86 (m, 2H), 2.53-2.50 (m, 1H), 2.20 (d, J=20 Hz, 2H), 1.88 (d, J=20 Hz, 2H), 1.59-1.46 (m, 4H); CI—MS (methane) (m/z): 296 [M+H]+; HRMS-API (m/z): [M+H]+ calcd for C20H25NO, 296.2014; found, 296.2015; HPLC: method A, 5.83 minutes (100%); method B, 10.56 minutes (96.5%); Analysis Calcd for C20H25NO.HCl.0.25H2O: C, 71.41; H, 7.94; N, 4.16. Found: C, 71.29; H, 7.66; N, 4.12.

Workup

  1. customThe reaction mixture was quenched with MeOH
  2. filtrationfiltered through Celite
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customPurification by flash chromatography (silica, 9:1 CH2Cl2:MeOH)
  5. customgave the free base which
  6. customRecrystallization from MeOH/Et2O

Sources & evidence

ORD record
ord-cbd682c043834c4aa6062f40be8e9f26
Source dataset
uspto-grants-2004_07
Patent number
US06765022B2

Reaction notes

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