(1R)-1-(2-Fluorophenyl)ethylamine → (+/-)-7-chloro-6-[1-(2-fluorophenyl)ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041271Notes

Reaction equation

HRID 2041271 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[F:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH:34]([NH2:36])[CH3:35]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:14])([F:15])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:36][CH:34]([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[F:27])[CH3:35]

Participants

4

Reactant 2

HCID 2782361(1R)-1-(2-Fluorophenyl)ethylamineHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 86629625(+/-)-7-chloro-6-[1-(2-fluorophenyl)ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 35%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Use a method similar to the General Procedure 5-1 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (250 mg, 0.6 mmol) with (±)-1-(2-fluorophenyl)-ethylamine (206 mg, 1.5 mmol) in toluene (5 mL). Purify the residue by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1) followed by SCX chromatography [pre-wash column with methanol followed by DCM, load material dissolved in DCM, then elute with DCM/2M ammonia in methanol (1:1) and concentrate in vacuo] to obtain (±)-7-chloro-6-[1-(2-fluorophenyl)-ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (86 mg, 35%). GC-MS m/z: 414 (M30 ).

Workup

  1. customPurify the residue by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1)
  2. washpre-wash column with methanol
  3. dissolutiondissolved in DCM
  4. washelute with DCM/2M ammonia in methanol (1:1)
  5. concentrationconcentrate in vacuo]

Sources & evidence

ORD record
ord-df26af10ca184bc495a14e2b1a243f99
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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