Cesium fluoride → (S)-(3,5-Bis-trifluoromethyl-benzyl)-(4-methyl-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine

HRID 507171Notes

Reaction equation

HRID 507171 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[CH2:6][N:7]([C@@H:14]1[C:20]2=[CH:21][C:22]3[CH2:23][O:24][CH2:25][C:26]=3[C:27](Br)=[C:19]2[NH:18][CH2:17][CH2:16][CH2:15]1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[F-].[Cs+].[CH3:40]B(O)O>O1CCOCC1.C(OCC)(=O)C.O>[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[CH2:6][N:7]([C@@H:14]1[C:20]2=[CH:21][C:22]3[CH2:23][O:24][CH2:25][C:26]=3[C:27]([CH3:40])=[C:19]2[NH:18][CH2:17][CH2:16][CH2:15]1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 139377Methylboronic AcidHCID 59432456(S)-(3,5-Bis-trifluoromethyl-benzyl)-(4-bromo-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine

Product 1

HCID 59432378(S)-(3,5-Bis-trifluoromethyl-benzyl)-(4-methyl-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of (S)-(3,5-Bis-trifluoromethyl-benzyl)-(4-bromo-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine (2.16 mmol) in dioxane (150 mL), add bis(diphenylphosphinoferrocene)palladium(II) chloride (0.22 mmol) followed by cesium fluoride (9.32 mmol) and methylboronic acid (6.48 mmol). Heat the mixture under nitrogen to 95° C. After heating for 2 h, cool the reaction mixture to room temperature and dilute with ethyl acetate (50 mL) and water (50 mL). Separate the organics and wash the aqueous with ethyl acetate (2×20 mL). Dry the combined organics over sodium sulfate, filter, and remove the solvent under vacuum. Chromatograph the crude product over silica gel, eluting with ethyl acetate/hexane (10-45%) to obtain the title compound as an off white solid. MS (ES+): 527 (M+H).

Workup

  1. temperatureAfter heating for 2 h
  2. temperaturecool the reaction mixture to room temperature
  3. customSeparate the organics and
  4. washwash the aqueous with ethyl acetate (2×20 mL)
  5. dry with materialDry the combined organics over sodium sulfate
  6. filtrationfilter
  7. customremove the solvent under vacuum
  8. washChromatograph the crude product over silica gel, eluting with ethyl acetate/hexane (10-45%)

Sources & evidence

ORD record
ord-90882338ee614929a866a71bfde43d41
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

Loading…