Hydrochloric Acid → (+/-)-7-Chloro-3-(2,2,2-trifluoroacetyl)-6-(2-phenyl-pyrrolidin-1-yl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1013123ノート

反応式

HRID 1013123 の反応式
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:19][CH2:20][CH2:21][CH2:22][C:23]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)OCCO1.CO.Cl.C([BH3-])#N.[Na+]>C(Cl)Cl.C(OCC)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:14])([F:15])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[N:19]1[CH2:20][CH2:21][CH2:22][CH:23]1[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 86622858HCID 86622858、化合物

生成物 1

HCID 59799052(+/-)-7-Chloro-3-(2,2,2-trifluoroacetyl)-6-(2-phenyl-pyrrolidin-1-yl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine収率 71%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒

実験手順

Dissolve 7-chloro-3-(2,2,2-trifluoroacetyl)-6-[3-(2-phenyl-[1,3]dioxolan-2-yl)-propylamino]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (2.78 g, 5.76 mmol) in DCM (25 mL) and add methanol (1 mL) and 2 N HCl in diethyl ether (25 mL) and stir at RT for 16 h. Concentrate and dissolve the residue in acetic acid (30 mL) and add sodium cyanoborohydride (1.81 g, 28.78 mmol). Stir the reaction at RT for 1 h then concentrate. Dissolve the residue in EtOAc (500 mL) and extract with saturated sodium bicarbonate solution (500 mL). Extract the aqueous layer with EtOAc (100 mL) and combine the organic fractions, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes) to give the title compound as a foam (1.72 g, 71%).

後処理

  1. concentrationConcentrate
  2. dissolutiondissolve the residue in acetic acid (30 mL)
  3. stirringStir
  4. customthe reaction at RT for 1 h
  5. concentrationthen concentrate
  6. dissolutionDissolve the residue in EtOAc (500 mL)
  7. extractionextract with saturated sodium bicarbonate solution (500 mL)
  8. extractionExtract the aqueous layer with EtOAc (100 mL)
  9. dry with materialdry (sodium sulfate)
  10. concentrationconcentrate
  11. custompurify
  12. wash(silica gel chromatography, eluting with 10:90 EtOAc:hexanes)

出典と根拠

ORDレコード
ord-1cbbc1bf8aa74e6eaa67101f5cb72779
出典データセット
uspto-grants-2011_07
特許番号
US07981882B2

反応ノート

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