Trifluoroacetic acid → Benzyl 1,2-dihydrospiro[indole-3,4'-piperidine]-1'-carboxylate

HRID 69085ノート

反応式

HRID 69085 の反応式
[C:1]1([NH:7]N)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O.[CH2:16]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([CH:32]=O)[CH2:28][CH2:27]1)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.C(#N)C.CO>[N:26]1([C:24]([O:23][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:25])[CH2:27][CH2:28][C:29]2([C:6]3[C:1](=[CH:2][CH:3]=[CH:4][CH:5]=3)[NH:7][CH2:32]2)[CH2:30][CH2:31]1

参加物

7

反応物 4

HCID 6422Trifluoroacetic acidHCID 7516PhenylhydrazineHCID 2776272Benzyl 4-formylpiperidine-1-carboxylateHCID 4311764Sodium borohydride

生成物 1

HCID 10914256Benzyl 1,2-dihydrospiro[indole-3,4'-piperidine]-1'-carboxylate収率 34.1%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 21584213Acetonitrile toluene溶媒2 回

反応条件

温度
35 °C

実験手順

A solution of phenyl hydrazine (1.29 g, 12.0 mmol) and trifluoroacetic acid (3.0 mL) in a 49/1 solution of toluene/acetonitrile (50 mL) is heated at 35° C. 4-Formyl-piperidine-1-carboxylic acid benzyl ester (2.7 g, 10.91 mmol) is dissolved in a 49/1 solution of toluene/acetonitrile (10 mL) and added dropwise to the mixture (WO2005046682). The mixture is stirred at 35° C. overnight. The resulting solution is cooled to 0° C., and methanol (5 mL) is added. NaBH4 (0.619 g, 16.38 mmol) is added slowly to the solution and the mixture is stirred for 45 min. The mixture is washed with aqueous NH4OH (6%, 25 mL) and brine (30 mL), dried over sodium sulfate, and evaporated to dryness to give a yellow solid. The crude solid is recrystallised from EtOAc to give a pale yellow solid (1.25 g, 1st crop). The mother liquor is evaporated and purified by flash chromatography, eluting with hexane:ethyl acetate (8:2) to give the title compound as a pale yellow solid (1.2 g, 2nd crop) with a total yield (2.4 g, 84%). ESI/MS m/z 323 (M+H)+.

後処理

  1. additionadded dropwise to the mixture (WO2005046682)
  2. temperatureThe resulting solution is cooled to 0° C.
  3. stirringthe mixture is stirred for 45 min
  4. washThe mixture is washed with aqueous NH4OH (6%, 25 mL) and brine (30 mL)
  5. dry with materialdried over sodium sulfate
  6. customevaporated to dryness
  7. customto give a yellow solid
  8. customThe crude solid is recrystallised from EtOAc
  9. customto give a pale yellow solid (1.25 g, 1st crop)
  10. customThe mother liquor is evaporated
  11. custompurified by flash chromatography
  12. washeluting with hexane:ethyl acetate (8:2)

出典と根拠

ORDレコード
ord-8322717fa1d54262ad32cb901b3a5e2b
出典データセット
uspto-grants-2014_09
特許番号
US08822486B2

反応ノート

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