3,5-Bis(trifluoromethyl)benzylamine → HCID 86616080, compound

HRID 2353956Notes

Reaction equation

HRID 2353956 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH2:11][C:10](=O)[C:9]2[C:15]([F:19])=[CH:16][CH:17]=[CH:18][C:8]1=2)=[O:6])([CH3:3])[CH3:2].[F:20][C:21]([F:35])([F:34])[C:22]1[CH:23]=[C:24]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:25][NH2:26]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:1]([O:4][C:5]([N:7]1[CH2:13][CH2:12][CH:11]=[C:10]([NH:26][CH2:25][C:24]2[CH:27]=[C:28]([C:30]([F:31])([F:32])[F:33])[CH:29]=[C:22]([C:21]([F:20])([F:34])[F:35])[CH:23]=2)[C:9]2[C:15]([F:19])=[CH:16][CH:17]=[CH:18][C:8]1=2)=[O:6])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 68677925HCID 68677925, compound

Product 1

HCID 86616080HCID 86616080, compoundYield 77.4%

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Procedure

Inject titanium isopropoxide (1.3 mL, 4.32 mmol) to a mixture of 6-fluor-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (572 mg, 2.16 mmol) and 3,5-bis(trifluoromethyl)benzylamine (972 mg, 3.2 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-2,3-dihydro-benzo[b]azepine-1-carboxylic isopropyl ester (820 mg, 77%). Add methanol (9.3 mL) and platinum oxide (37 mg, 0.16 mmol) to 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-2,3-dihydro-benzo[b]azepine-1-carboxylic isopropyl ester (742 mg, 1.5 mmol) and hydrogenate the mixture at 1 atmosphere and room temperature for 2 h. Filter through celite and remove the solvent under reduced pressure to afford 5-(3,5-Bis-trifluoromethyl-benzylamino)-6-fluoro-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (730 mg, quantitative). Add acetic anhydride (0.5 mL, 5.78 mmol) dropwise to a suspension of the amine (190 mg, 0.385 mmol) and pyridine (0.5 mL, 5.78 mmol) in dichloromethane (1.5 mL), stir under nitrogen at room temperature for 14 h. Add 1 M hydrochloric acid and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (141 mg, 68%); MS (ES+): 535 (M+H).

Workup

  1. customPurify the residue by flash chromatography
  2. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-4646046bec1544029b4da6e405b7064f
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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