Dichloromethane → HCID 178483270, compound

HRID 1884517Notes

Reaction equation

HRID 1884517 reaction equation
[C:1]1([C@H:7]2[CH2:12][CH2:11][C@H:10]([NH:13][CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:23](Cl)Cl.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>CO.O>[CH3:23][N:13]([C@H:10]1[CH2:9][CH2:8][C@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:12][CH2:11]1)[CH2:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride3×HCID 178516031HCID 178516031, compound

Product 1

HCID 178483270HCID 178483270, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirred solution of trans-4-[2-(4-phenylcyclohexylamino)ethyl]phenol (380 mg, 1.3 mmol) in MeOH (5 mL), H2O (0.5 mL), and CH2Cl2 (5 mL) was added ρformaldehyde (200 mg, 6.5 mmol). After stirring for 15 minutes NaBH(OAc)3 (340 mg, 1.6 mmol) was added, and the reaction mixture was stirred for 12 hours. Additional NaBH(OAc)3 (138 mg, 0.65 mmol) was added, and the mixture was stirred for 2 days. NaBH(OAc)3 (138 mg, 0.65 mmol) was added, and stirring was continued for 6 hours. Solid NaOH was added to give a clear solution, which was concentrated under reduced pressure. Purification by flash chromatography (silica, 89:10:1 CH2Cl2:MeOH:NH4OH) and formation of the HCl salt gave trans-4-{2-[methyl(4-phenylcyclohexyl)amino]ethyl}phenol (380 mg, 64%), as an off-white solid: mp 97-105° C.; IR (KBr): 2941, 1614, 1517 cm−1; 1H NMR (500 MHz, DMSO-d6) δ 11.05 (s, 1H), 9.42 (s, 1H), 7.35-7.15 (m, 5H), 7.10 (br d, J=8 Hz, 2H), 6.77 (br d, J=8 Hz, 2H), 3.49-2.94 (m, 6H), 2.80-2.70 (m, 2H), 2.56-2.48 (m, 1H), 2.30-2.11 (m, 2H), 1.89 (br d, J=11.5 Hz, 2H), 1.75-1.50 (m, 4H); CI—MS (methane) (m/z): 310 [M+H]+; HPLC: method A, 5.99 minutes (99.4%); method B, 10.68 minutes (99.1%); Anal. Calcd for C21H27NO.HCl.0.25H2O: C, 71.98; H, 8.20; N, 4.00. Found: C, 71.60; H, 8.31; N, 3.86.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for 2 days
  3. stirringstirring
  4. waitwas continued for 6 hours
  5. customto give a clear solution, which
  6. concentrationwas concentrated under reduced pressure
  7. customPurification by flash chromatography (silica, 89:10:1 CH2Cl2:MeOH:NH4OH) and formation of the HCl salt

Sources & evidence

ORD record
ord-32f8229011d9416c98c58409d3cb7d8e
Source dataset
uspto-grants-2004_07
Patent number
US06765022B2

Reaction notes

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