Isobutyraldehyde trimethylsilyl enol ether → [4-(2-hydroxy-1,1-dimethyl-ethyl)-3-methoxy-phenyl]-(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]-1'-yl)methanone

HRID 1908178

반응식

HRID 1908178 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][C:13]3([C:27]4[CH:26]=[N:25][N:24]([CH3:28])[C:23]=4[C:22]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[O:16]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[O:29][CH3:30].C[Si](C)(C)[O:33][CH:34]=[C:35]([CH3:37])[CH3:36].[BH4-].[Na+]>CN(C=O)C.F[Zn]F>[OH:33][CH2:34][C:35]([C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][C:13]3([C:27]4[CH:26]=[N:25][N:24]([CH3:28])[C:23]=4[C:22]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[O:16]3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[O:29][CH3:30])([CH3:37])[CH3:36]

참가 물질

6

반응물 3

HCID 99685Isobutyraldehyde trimethylsilyl enol etherHCID 4311764Sodium borohydrideHCID 58551290(4-bromo-3-methoxyphenyl)(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]-1'-yl)methanone

생성물 1

HCID 58550911[4-(2-hydroxy-1,1-dimethyl-ethyl)-3-methoxy-phenyl]-(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]-1'-yl)methanone

시약·촉매·용매 2

HCID 24551Zinc fluoride촉매HCID 6228Dimethylformamide용매

실험 절차

To a microwave vial was added difluorozinc (16 mg, 0.15 mmol) and Pd(tBu3P)2 (7.6 mg, 0.015 mmol). The vial was capped and purged with nitrogen for 10 minutes. DMF (1 mL) was added and the reaction mixture was allowed to stir for 10 minutes. (4-Bromo-3-methoxyphenyl)(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]-1′-yl)methanone (140 mg, 0.30 mmol) dissolved in DMF (0.5 mL) was added followed by trimethyl(2-methylprop-1-enoxy)silane (83 μL, 0.45 mmol). The reaction vessel was placed in an oil bath held at 80° C. for 16 hours. The reaction mixture was filtered, quenched with brine and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and evaporated to dryness. The residue was dissolved in MeOH (2 mL). NaBH4 (34 mg, 0.90 mmol) was added and the reaction mixture immediately turned from yellow to brown. The mixture was filtered and purified by HPLC (1-99%) MeOH:H2O to provide [4-(2-hydroxy-1,1-dimethyl-ethyl)-3-methoxy-phenyl]-(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]-1′-yl)methanone. ESI-MS m/z calc. 461.5. found 462.2 (M+1)+. Retention time: 2.73 minutes (4 min run).

후처리

  1. customThe vial was capped
  2. custompurged with nitrogen for 10 minutes
  3. additionDMF (1 mL) was added
  4. additionwas added
  5. customThe reaction vessel was placed in an oil bath
  6. waitheld at 80° C. for 16 hours
  7. filtrationThe reaction mixture was filtered
  8. customquenched with brine
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic layer was dried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated to dryness
  13. dissolutionThe residue was dissolved in MeOH (2 mL)
  14. filtrationThe mixture was filtered
  15. custompurified by HPLC (1-99%) MeOH

출처 및 근거

ORD 기록
ord-8e16611493444e15b3e953578e247312
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598164B2

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