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 507070노트

반응식

HRID 507070 반응식
[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]

참가 물질

7

반응물 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

생성물 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 ester수율 83%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 887Methanol용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-d8b0dc6ca0ec4dc3bcbdd559a0285caa
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786108B2

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