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 2204273

反応式

HRID 2204273 の反応式
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]

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 24551Zinc fluoride触媒HCID 6228Dimethylformamide溶媒

実験手順

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 talc. 461.5, found 462.2 (M+1)+. Retention time: 2.73 minutes (4 min run).

後処理

  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

出典と根拠

ORDレコード
ord-27823a3475b24064a13f9b017ac4479f
出典データセット
uspto-grants-2016_06
特許番号
US09365588B2

関連ノート

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