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Trifluoroacetic acid → benzyl 1-ethyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]-1'-carboxylate

HRID 2204112
ノート
印刷プレビュー

反応式

HRID 2204112 の反応式
[CH2:1]([N:3](C(OC(C)(C)C)=O)[NH2:4])[CH3:2].O[CH:13]=[C:14]1[C:23]2([CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:30])[CH2:25][CH2:24]2)[O:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]1=O.C(O)(C(F)(F)F)=O.NN>ClC(Cl)C.ClCCl.C(=O)(O)[O-].[Na+]>[CH2:1]([N:3]1[C:15]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=3[O:22][C:23]3([CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[O:30])[CH2:25][CH2:24]3)[C:14]=2[CH:13]=[N:4]1)[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

8

反応物 4

HCID 6422Trifluoroacetic acid2 回HCID 9321HydrazineHCID 57517432N-ethyl(tert-butoxy)carbohydrazideHCID 67463745Benzyl 3-(hydroxymethylene)-4-oxo-spiro[chromane-2,4'-piperidine]-1'-carboxylate

生成物 1

HCID 58551072benzyl 1-ethyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]-1'-carboxylate収率 65.7%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 63651,1-Dichloroethane溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

A mixture of tert-butyl 1-ethylhydrazinecarboxylate (320 mg, 2.0 mmol) and benzyl 3-(hydroxymethylene)-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (770 mg, 2.0 mmol) in dichloroethane (5 mL) was allowed to stir at 25° C. with TFA (78 μL, 1.0 mmol) for 2 h. Once LC/MS analysis showed complete imine formation, more TFA was added to deprotect the hydrazine and cyclize the product. The reaction was diluted with dichloromethane, and aqueous sodium bicarbonate was added with stirring. The layers were separated and the organics were further washed with saturated aqueous sodium bicarbonate and brine. The organics were dried over sodium sulfate and evaporated to dryness. The crude material was purified by column chromatography (0-100% ethyl acetate in hexanes) to afford benzyl 1-ethyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]-1′-carboxylate (530 mg, 65%). ESI-MS m/z calc. 403.2, found 404.7 (M+1)+; Retention time: 1.94 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J=7.6 Hz, 1H), 7.40-7.29 (m, 4H), 7.29-7.19 (m, 2H), 7.10-6.99 (m, 2H), 5.16 (s, 2H), 4.47 (q, J=7.3 Hz, 2H), 4.15-3.95 (m, 2H), 3.45-3.26 (m, 2H), 2.15-2.03 (m, 2H), 1.88-1.78 (m 2H), 1.54 (t, J=7.3 Hz, 4H).

後処理

  1. additionwas added
  2. additionwas added
  3. customThe layers were separated
  4. washthe organics were further washed with saturated aqueous sodium bicarbonate and brine
  5. dry with materialThe organics were dried over sodium sulfate
  6. customevaporated to dryness
  7. customThe crude material was purified by column chromatography (0-100% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-47e273391b1e4665b12b8be985b0ee77
出典データセット
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09365588B2

反応ノート

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