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Sodium Hydroxide → (+/-)-5-(3,5-Bis-trifluoromethyl-benzylamino)-6-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

HRID 2353945
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HRID 2353945 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[CH2:29][CH2:28][CH2:27][C:26](=O)[C:25]2[C:31]([CH3:35])=[CH:32][CH:33]=[CH:34][C:24]1=2)=[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[CH2:29][CH2:28][CH2:27][CH:26]([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)[C:25]2[C:31]([CH3:35])=[CH:32][CH:33]=[CH:34][C:24]1=2)=[O:22])([CH3:19])[CH3:18]
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참가 물질

7

반응물 4

HCID 14798Sodium HydroxideHCID 5210993,5-Bis(trifluoromethyl)benzylamineHCID 4311764Sodium borohydrideHCID 59003235HCID 59003235, 화합물

생성물 1

HCID 86616077(+/-)-5-(3,5-Bis-trifluoromethyl-benzylamino)-6-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester수율 3.4%

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매
HCID 887Methanol용매

실험 절차

Add 3,5-bis(trifluoromethyl)benzylamine (423 mg, 1.62 mmol) followed by titanium isopropoxide (645 mg, 2.27 mmol) to 6-Methyl-5-oxo-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (423 mg, 1.62 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Add methanol (6.7 mL) and sodium borohydride (92 mg, 2.43 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 (+/−)-5-(3,5-Bis-trifluoromethyl-benzylamino)-6-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (27 mg, 3%). Add acetic anhydride (0.037 mL, 0.39 mmol) dropwise to a solution of the amine (27 mg, 0.055 mmol) and pyridine (0.038 mL, 0.43 mmol) in dichloromethane (0.5 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 (28 mg, 96%); MS (ES+): 531 (M+H).

후처리

  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

출처 및 근거

ORD 기록
ord-096c37ff56f646688e81130c5c1564f0
출처 데이터셋
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07749992B2

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