Triethylamine → Benzyl 1'-methylspiro[indoline-3,4'-piperidine]-1-carboxylate

HRID 849552ノート

反応式

HRID 849552 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][CH2:8]2)[CH2:4][CH2:3]1.CCN(CC)CC.Cl[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25]>C(Cl)Cl>[CH2:27]([O:26][C:24]([N:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]2([CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)[CH2:8]1)=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

参加物

5

反応物 3

HCID 8471Triethylamine3 回HCID 10387Benzyl chloroformate3 回HCID 128015871'-Methylspiro[indoline-3,4'-piperidine]

生成物 1

HCID 10711919Benzyl 1'-methylspiro[indoline-3,4'-piperidine]-1-carboxylate収率 71.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of 99 g (489 mmol) of 1'-methylspiro(indoline-3,4'-piperidine) (prepared according to Ong, H. H. et al, J. Med. Chem., 1983, 26, 981-986) in 1 L of CH2Cl2 and 82 mL (539 mmol) of Et3N was cooled to 0-5° C. with an ice bath and 77 mL (539 mmol) of benzyl chloroformate was added over 30 min keeping the reaction temperature below 10° C. After stirring for 2 h 19 mL (136 mmol) of Et3N and 15 mL (105 mmol) of benzyl chloroformate were added since the reaction was incomplete and stirred for 2 h. At this time, additional 19 mL (136 mmol) of Et3N and 15 mL (105 mmol) of benzyl chloroformate were added. After 1 h, when a TLC indicated a complete reaction, the solution was concentrated in vacuo and the residue was partitioned between ether and saturated NaHCO3. The layers were separated, the organic layer was washed with saturated NaHCO3 and brine, and dried over MgSO4. The filtrate was concentrated and the residue was chromatographed on 2 kg of silica gel using 1-5% MeOH/CH2Cl2 to obtain 117 g (71%) of 1-benzyloxycarbonyl-1'-methylspiro(indoline-3,4'-piperidine) as a yellow oil.

後処理

  1. customthe reaction temperature below 10° C
  2. additionwere added since the reaction
  3. waitAfter 1 h
  4. customa complete reaction
  5. concentrationthe solution was concentrated in vacuo
  6. customthe residue was partitioned between ether and saturated NaHCO3
  7. customThe layers were separated
  8. washthe organic layer was washed with saturated NaHCO3 and brine
  9. dry with materialdried over MgSO4
  10. concentrationThe filtrate was concentrated
  11. customthe residue was chromatographed on 2 kg of silica gel using 1-5% MeOH/CH2Cl2

出典と根拠

ORDレコード
ord-72ea82e1cff0456a8fa3714f912b84e4
出典データセット
uspto-grants-2000_01
特許番号
US06013652

反応ノート

読み込み中…