Cesium fluoride → (S)-(3-chloro-5-trifluoromethyl-benzyl)-(7,9-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 507181Notes

Reaction equation

HRID 507181 reaction equation
Br[C:2]1[C:7]2[NH:8][CH2:9][CH2:10][CH2:11][C@H:12]([N:13]([CH2:20][C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([Cl:31])[CH:22]=3)[C:14]3[N:15]=[N:16][N:17]([CH3:19])[N:18]=3)[C:6]=2[CH:5]=[C:4]([CH3:32])[C:3]=1[C:33]([F:36])(F)[F:34].[CH3:37]B(O)O.[F-:41].[Cs+]>O1CCOCC1.C(OCC)(=O)C.[Cl-].[Cl-].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].[Pd+2]>[Cl:31][C:23]1[CH:22]=[C:21]([CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=1)[CH2:20][N:13]([C@H:12]1[CH2:11][CH2:10][CH2:9][NH:8][C:7]2[C:2]([CH3:37])=[C:3]([C:33]([F:34])([F:36])[F:41])[C:4]([CH3:32])=[CH:5][C:6]1=2)[C:14]1[N:15]=[N:16][N:17]([CH3:19])[N:18]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 139377Methylboronic AcidHCID 59432411(S)-(9-bromo-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(3-chloro-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amine

Product 1

HCID 59432530(S)-(3-chloro-5-trifluoromethyl-benzyl)-(7,9-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amineYield 92.4%

Reagents, catalysts & solvents 3

HCID 178478644HCID 178478644, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Add a solution of (S)-(9-bromo-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(3-chloro-5-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amine (0.39 g, 0.65 mmol) in dioxane (5 mL) to a mixture of methylboronic acid (0.12 g, 1.96 mmol), palladium diphenylphosphinoferrocene dichloride (0.05 g, 0.06 mmol), and cesium fluoride (0.35 g, 2.32 mmol), then purge with nitrogen and stir for 15 min. at room temperature, then at 100° C. for 4 h. After completion, cool the reaction to room temperature, dilute with ethyl acetate (50 mL) and wash with water and brine (10 mL each). Dry the organic layer over sodium sulfate, filter, and remove the solvent under reduced pressure. Purify the residue using flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (0-30% EtOAc in hexane), to provide the title compound as a white solid (0.32 g, 90%). MS (ES+): 533 (M+H).

Workup

  1. custompurge with nitrogen
  2. waitat 100° C. for 4 h
  3. temperatureAfter completion, cool
  4. customthe reaction to room temperature
  5. washwash with water and brine (10 mL each)
  6. dry with materialDry the organic layer over sodium sulfate
  7. filtrationfilter
  8. customremove the solvent under reduced pressure
  9. customPurify the residue
  10. washeluting with hexanes/ethyl acetate (0-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-0e19c3b446a44ceba82668720c7e4855
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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