2-甲基-1-(三甲基硅氧基)-1-丙烯 → [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笔记

反应方程式

HRID 1908178 反应方程式
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]

参与物

6

反应物 3

HCID 996852-甲基-1-(三甲基硅氧基)-1-丙烯HCID 4311764硼氢化钠HCID 58551290(4-bromo-3-methoxyphenyl)(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4'-piperidine]-1'-yl)methanone

产物 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

试剂、催化剂与溶剂 2

HCID 24551氟化锌催化剂HCID 6228N,N-二甲基甲酰胺溶剂

实验过程

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).

后处理

  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

来源与证据

ORD记录
ord-8e16611493444e15b3e953578e247312
来源数据集
uspto-grants-2013_12
专利号
US08598164B2

反应笔记

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