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Hydrochloric Acid → (+/-)-9-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester

HRID 2353929
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HRID 2353929 반응식
[C:1](OC(=O)C)(=[O:3])[CH3:2].[CH:8]([O:11][C:12]([N:14]1[C:27]2[C:19](=[CH:20][C:21]3[CH2:22][CH2:23][CH2:24][C:25]=3[CH:26]=2)[CH:18]([NH:28][CH2:29][C:30]2[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[C:32]([C:40]([F:43])([F:42])[F:41])[CH:31]=2)[CH2:17][CH2:16][CH2:15]1)=[O:13])([CH3:10])[CH3:9].N1C=CC=CC=1.Cl>ClCCl>[CH:8]([O:11][C:12]([N:14]1[C:27]2[C:19](=[CH:20][C:21]3[CH2:22][CH2:23][CH2:24][C:25]=3[CH:26]=2)[CH:18]([N:28]([C:1](=[O:3])[CH3:2])[CH2:29][C:30]2[CH:31]=[C:32]([C:40]([F:43])([F:41])[F:42])[CH:33]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:35]=2)[CH2:17][CH2:16][CH2:15]1)=[O:13])([CH3:10])[CH3:9]
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참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 86615658(+/-)-9-(3,5-bis-trifluoromethyl-benzylamino)-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester

생성물 1

HCID 59003114(+/-)-9-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester
수율 74.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Add 3,5-bis(trifluoromethyl)benzylamine (187 mg, 0.77 mmol) followed by titanium isopropoxide (835 mg, 2.94 mmol) to 9-Oxo-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester (200 mg, 0.7 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 3 days. Add methanol (3 mL) and sodium borohydride (40 mg, 1.05 mmol) and stir the mixture under nitrogen at room temperature for 16 hours. Add sodium bicarbonate saturated solution. 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 silica cartridge, eluting with hexanes/ethyl acetate 9:1, to afford of (+/−)-9-(3,5-bis-trifluoromethyl-benzylamino)-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester (220 mg). Add acetic anhydride (0.22 mL, 2.33 mmol) dropwise to a solution of the amine (80 mg, 0.155 mmol) and pyridine (0.18 mL, 2.33 mmol) in dichloromethane (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 silica gel cartridge, eluting with hexanes/ethyl acetate 4:1, to afford the title compound (64 mg, 74%); MS (ES+): 579 (M+H+Na).

후처리

  1. extractionextract with dichloromethane
  2. dry with materialDry the organic layer over anhydrous sodium sulfate
  3. filtrationfilter
  4. customremove the solvent under reduced pressure
  5. customPurify the residue by silica gel cartridge
  6. washeluting with hexanes/ethyl acetate 4:1

출처 및 근거

ORD 기록
ord-f4d262b2293741d5a2ee1399849fa2e1
출처 데이터셋
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07749992B2

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