Methylamine → HCID 53323814, compound

HRID 333272Notes

Reaction equation

HRID 333272 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:15](=O)[CH3:16])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].CN.[BH3-][C:21]#[N:22].[Na+]>[Ti+4]>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH:15]([NH:22][CH3:21])[CH3:16])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 5003444Sodium cyanoborohydrideHCID 58954812HCID 58954812, compound

Product 1

HCID 53323814HCID 53323814, compoundYield 4.4%

Reagents, catalysts & solvents 1

HCID 114942Titanium cation (4+)Catalyst

Procedure

A mixture of 1-(1-(3,4-dichlorophenyl)cyclohexyl)ethanone (247 mg, 0.91 mmol) and methyl amine (455 μL, 2.0 M in THF, 0.91 mmol) was stirred at RT for 2 min. Titanium (IV) isoproxide (336 μL, 1.14 mmol) was then added. The viscous green/yellow solution was stirred at RT for 3 h. NaBH3CN solution (640 μL, 1.0 M in MeOH, 0.64 mmol) was added and the cloudy solution was stirred at RT for 16 h. The solution was quenched with saturated NaCl solution (3 mL), filtered, and washed with MeOH (50 mL). 6M HCl (20 mL) was added and the aqueous phase was washed with Et2O (2×20 mL). The pH of the aqueous phase was adjusted to pH=12 with 3M NaOH and washed with EtOAc (3×30 mL). The combined organic phases were dried (Na2SO4), filtered and concentrated. To a solution of the crude amine in Et2O (3 mL) was added HCl (3 mL, 2.0 M in Et2O). The crude HCl salt was recrystallized from CH3CN (6 mL) at 110° c to give 1-(1-(3,4-dichlorophenyl)cyclohexyl)-N-methylethanamine (8 mg) as white crystals. HPLC Rt=8.90 min; 1H NMR (400 mHz, CD3OD) 7.57-7.53 (m, 2H), 7.33-7.31 (m, 1H), 3.15-3.13 (m, 2H), 2.61 (s, 3H), 2.45 (broad d, J=11.73 Hz, 1H), 2.30 (broad d, J=12.46, 1H), 1.59-1.51 (m, 5H), 1.31-1.08 (m, 6H); LC-MS 7.87 min, (M+1) 286 @ 8.10 min.

Workup

  1. stirringThe viscous green/yellow solution was stirred at RT for 3 h
  2. stirringthe cloudy solution was stirred at RT for 16 h
  3. customThe solution was quenched with saturated NaCl solution (3 mL)
  4. filtrationfiltered
  5. washwashed with MeOH (50 mL)
  6. addition6M HCl (20 mL) was added
  7. washthe aqueous phase was washed with Et2O (2×20 mL)
  8. washwashed with EtOAc (3×30 mL)
  9. dry with materialThe combined organic phases were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. additionTo a solution of the crude amine in Et2O (3 mL) was added HCl (3 mL, 2.0 M in Et2O)
  13. customThe crude HCl salt was recrystallized from CH3CN (6 mL) at 110° c

Sources & evidence

ORD record
ord-c408d96133f04a4eb88c9d623b8ebb3c
Source dataset
uspto-grants-2014_11
Patent number
US08877975B2

Reaction notes

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