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 507181ノート

反応式

HRID 507181 の反応式
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

参加物

7

反応物 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

生成物 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)-amine収率 92.4%

試薬・触媒・溶媒 3

HCID 178478644HCID 178478644、化合物触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-0e19c3b446a44ceba82668720c7e4855
出典データセット
uspto-grants-2010_08
特許番号
US07786108B2

反応ノート

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