Sodium Hydroxide → (+/-)-6-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester

HRID 2353939ノート

反応式

HRID 2353939 の反応式
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[CH2:6][NH2:7].[CH:17]([O:20][C:21]([N:23]1[C:29]2[C:30]3[CH2:31][CH2:32][CH2:33][C:34]=3[CH:35]=[CH:36][C:28]=2[C:27](=O)[CH2:26][CH2:25][CH2:24]1)=[O:22])([CH3:19])[CH3:18].[BH4-].[Na+].[OH-].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CO>[CH:17]([O:20][C:21]([N:23]1[C:29]2[C:30]3[CH2:31][CH2:32][CH2:33][C:34]=3[CH:35]=[CH:36][C:28]=2[CH:27]([NH:7][CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:15])([F:16])[F:1])[CH:10]=[C:9]([C:11]([F:14])([F:12])[F:13])[CH:8]=2)[CH2:26][CH2:25][CH2:24]1)=[O:22])([CH3:19])[CH3:18]

参加物

7

反応物 4

HCID 14798Sodium HydroxideHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydrideHCID 593791336-Oxo-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester

生成物 1

HCID 86615657(+/-)-6-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester収率 83%

試薬・触媒・溶媒 2

HCID 11026Titanium isopropoxide触媒HCID 887Methanol溶媒

実験手順

Add 3,5-bis(trifluoromethyl)benzylamine (349 mg, 1.15 mmol) followed by titanium isopropoxide (414 mg, 1.46 mmol) to 6-Oxo-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester (300 mg, 1.04 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Add methanol (4.3 mL) and sodium borohydride (59 mg, 1.56 mmol) and stir the mixture under nitrogen at room temperature for 45 min. Add 0.1M NaOH, stir for 30 min. Filter through celite and wash the residue with AcOEt. Separate organic layer, extract aqueous with AcOEt. Wash organic layer with brine and dry the organic layers over anhydrous sodium sulfate. Filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford (+/−)-6-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester (443 mg, 83%). Add acetic anhydride (0.24 mL, 2.52 mmol) dropwise to a solution of the amine (184 mg, 0.36 mmol) and pyridine (0.25 mL, 3.06 mmol) in dichloromethane (3.1 mL). Stir under nitrogen at room temperature for 14 h. Add 1 M hydrochloric acid and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (149 mg, 74%); MS (ES+): 557 (M+H).

後処理

  1. stirringstir for 30 min
  2. filtrationFilter through celite
  3. washwash the residue with AcOEt
  4. extractionSeparate organic layer, extract aqueous with AcOEt
  5. dry with materialWash organic layer with brine and dry the organic layers over anhydrous sodium sulfate
  6. filtrationFilter
  7. customremove the solvent under reduced pressure
  8. customPurify the residue by flash chromatography
  9. washeluting with hexanes/ethyl acetate

出典と根拠

ORDレコード
ord-1892bff6c4c14c18816de3895d4eefa5
出典データセット
uspto-grants-2010_07
特許番号
US07749992B2

反応ノート

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