Tert-butyl N-(4-(aminomethyl)phenyl)carbamate → 6-(4-tert-butoxycarbonylamino-benzylamino)-7-chloro-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]-azepine

HRID 1191034Notes

Reaction equation

HRID 1191034 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.[C:27]([O:31][C:32]([NH:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39][NH2:40])=[CH:37][CH:36]=1)=[O:33])([CH3:30])([CH3:29])[CH3:28]>C1(C)C=CC=CC=1.O1CCOCC1>[C:27]([O:31][C:32]([NH:34][C:35]1[CH:36]=[CH:37][C:38]([CH2:39][NH:40][C:3]2[C:4]3[CH2:10][CH2:9][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:7][CH2:6][C:5]=3[CH:17]=[CH:18][C:2]=2[Cl:1])=[CH:41][CH:42]=1)=[O:33])([CH3:30])([CH3:28])[CH3:29]

Participants

4

Reactant 2

HCID 2794659Tert-butyl N-(4-(aminomethyl)phenyl)carbamateHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 584956276-(4-tert-butoxycarbonylamino-benzylamino)-7-chloro-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]-azepineYield 89.3%

Reagents, catalysts & solvents 1

HCID 21840791Dioxane tolueneSolvent

Procedure

Use a method similar to the General Procedure 1-3 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.32 g, 0.76 mmol) with a solution of 4-(tert-butoxycarbonylamino)-benzylamine (0.338 g, 1.524 mmol) in anhydrous toluene/dioxane (4:1, 10 mL). Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 3:1 gradient over 30 min; 3:1 over 3 min; 3:1 to 1:1 gradient over 30 min and 1:1 over 3 min; 35 mL/min) to obtain the desired intermediate as a yellow oil (0.338 g, 89%). MS (ES+) m/z: 498.2 (M+H)+.

Workup

  1. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (1:0 to 3:1 gradient over 30 min; 3:1 over 3 min; 3:1 to 1:1 gradient over 30 min and 1:1 over 3 min; 35 mL/min)

Sources & evidence

ORD record
ord-3c145300c9b44d039a4bf734b9e675fb
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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