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Hydrochloric Acid → (+/-)-Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-6-methyl-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353946
ノート
印刷プレビュー

反応式

HRID 2353946 の反応式
[C:1](OC(=O)C)(=[O:3])[CH3:2].[CH:8]([O:11][C:12]([N:14]1[CH2:20][CH2:19][CH2:18][CH:17]([NH:21][CH2:22][C:23]2[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=2)[C:16]2[C:37]([CH3:41])=[CH:38][CH:39]=[CH:40][C:15]1=2)=[O:13])([CH3:10])[CH3:9].N1C=CC=CC=1.Cl>ClCCl>[C:1]([N:21]([CH2:22][C:23]1[CH:28]=[C:27]([C:29]([F:30])([F:32])[F:31])[CH:26]=[C:25]([C:33]([F:34])([F:35])[F:36])[CH:24]=1)[CH:17]1[CH2:18][CH2:19][CH2:20][N:14]([C:12]([O:11][CH:8]([CH3:10])[CH3:9])=[O:13])[C:15]2[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[C:16]1=2)(=[O:3])[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 86616077(+/-)-5-(3,5-Bis-trifluoromethyl-benzylamino)-6-methyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester

生成物 1

HCID 59003181(+/-)-Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-6-methyl-tetrahydrobenzo[b]azepine-1-carboxylate収率 96%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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 flash chromatography
  6. washeluting with hexanes/ethyl acetate

出典と根拠

ORDレコード
ord-e49c6261fc42452bb122da6dec0ac5a7
出典データセット
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07749992B2

反応ノート

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