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 507070ノート

反応式

HRID 507070 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 and stir for 30 min. Filter through Celite® and wash the residue with ethyl acetate. Separate the organic layer and extract the aqueous with ethyl acetate. Wash the 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 (+/−)isopropyl-6-(3,5-bis-trifluoromethyl-benzylamino)-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylate (443 mg, 83%).

後処理

  1. stirringstir for 30 min
  2. filtrationFilter through Celite®
  3. washwash the residue with ethyl acetate
  4. customSeparate the organic layer
  5. extractionextract the aqueous with ethyl acetate
  6. washWash the organic layer with brine
  7. dry with materialdry the organic layers over anhydrous sodium sulfate
  8. filtrationFilter
  9. customremove the solvent under reduced pressure
  10. customPurify the residue by flash chromatography
  11. washeluting with hexanes/ethyl acetate

出典と根拠

ORDレコード
ord-d8b0dc6ca0ec4dc3bcbdd559a0285caa
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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