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

HRID 1908027
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HRID 1908027 반응식
[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]
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참가 물질

8

반응물 4

HCID 6422Trifluoroacetic acid2회HCID 9321HydrazineHCID 57517432N-ethyl(tert-butoxy)carbohydrazideHCID 67463745Benzyl 3-(hydroxymethylene)-4-oxo-spiro[chromane-2,4'-piperidine]-1'-carboxylate

생성물 1

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

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 63651,1-Dichloroethane용매HCID 516892Sodium Bicarbonate용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1aa2059fa17941fd810df3ee39269875
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08598164B2

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