Hydrochloric Acid → Methyl 6-(4,4,4-trifluoro-1-(4'-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinate

HRID 2173867Notes

Reaction equation

HRID 2173867 reaction equation
Cl.C(OCC)C.C(OC([N:14]([CH:25]([C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][CH:39]=2)=[CH:34][CH:33]=1)[CH2:26][CH2:27][C:28]([F:31])([F:30])[F:29])[C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][N:16]=1)=O)(C)(C)C>ClCCl>[F:31][C:28]([F:29])([F:30])[CH2:27][CH2:26][CH:25]([NH:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][N:16]=1)[C:32]1[CH:33]=[CH:34][C:35]([C:38]2[CH:39]=[CH:40][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:43]=2)=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 86667303Methyl 6-(tert-butoxycarbonyl(4,4,4-trifluoro-1-(4'-(trifluoromethyl)biphenyl-4-yl)butyl)amino)nicotinate

Product 1

HCID 86667304Methyl 6-(4,4,4-trifluoro-1-(4'-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinateYield 73.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 2M solution of HCl in diethyl ether (1 mL, 2 mmol) was added to a room temperature solution of methyl 6-(tert-butoxycarbonyl(4,4,4-trifluoro-1-(4′-(trifluoromethyl)biphenyl-4-yl)butyl)amino)nicotinate (30 mg, 0.051 mmol) in 1 mL dichloromethane. After 18 h, the solution was concentrated and the residue redissolved in 2 mL trifluoroacetic acid. After 2 h, the solution was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was dried over MgSO4 and concentrated to give methyl 6-(4,4,4-trifluoro-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinate (18 mg, 73%) as a colorless film. 1H NMR (400 MHz, CDCl3) 8.72-8.74 (m, 1H), 7.94 (dd, J=8 Hz, 2.5 Hz, 2H), 7.61-7.70 (m, 4H), 7.57 (d, J=8.2 Hz, 2H), 7.42 (d, J=8.2 Hz, 2H), 6.29 (d, J=8.8 Hz, 1H), 5.40 (d, J=7.6 Hz, 1H), 4.90-5.01 (m, 1H), 3.83 (s, 3H), 2.06-2.36 (m, 4H).

Workup

  1. concentrationthe solution was concentrated
  2. dissolutionthe residue redissolved in 2 mL trifluoroacetic acid
  3. waitAfter 2 h
  4. concentrationthe solution was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washwashed with saturated aqueous sodium bicarbonate
  7. dry with materialThe organic layer was dried over MgSO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9cc23665e68e43f29fd5779da4d81a6d
Source dataset
uspto-grants-2015_06
Patent number
US09056834B2

Reaction notes

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