tert-Butyl 4-ethenylpiperidine-1-carboxylate → Tert-butyl 4-(3-(6-(4-methoxybenzylcarbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)piperidine-1-carboxylate

HRID 572649Notes

Reaction equation

HRID 572649 reaction equation
[OH:1][N:2]=[CH:3][C:4]1[N:9]=[C:8]([CH3:10])[N:7]=[C:6]([C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[O:12])[CH:5]=1.[CH:23]([CH:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)=[CH2:24].C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>C(Cl)(Cl)Cl>[CH3:22][O:21][C:18]1[CH:17]=[CH:16][C:15]([CH2:14][NH:13][C:11]([C:6]2[N:7]=[C:8]([CH3:10])[N:9]=[C:4]([C:3]3[CH2:24][CH:23]([CH:25]4[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:29][CH2:30]4)[O:1][N:2]=3)[CH:5]=2)=[O:12])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 10910832tert-Butyl 4-ethenylpiperidine-1-carboxylateHCID 12217721Iodo benzene diacetateHCID 1364132316-((hydroxyimino)methyl)-N-(4-methoxybenzyl)-2-methylpyrimidine-4-carboxamide

Product 1

HCID 86675906Tert-butyl 4-(3-(6-(4-methoxybenzylcarbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)piperidine-1-carboxylateYield 29.7%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a cold solution of (6-((hydroxyimino)methyl)-N-(4-methoxybenzyl)-2-methylpyrimidine-4-carboxamide (0.2 g, 0.66 mmol, Preparation #B.1.1) and tert-butyl 4-vinylpiperidine-1-carboxylate (0.168 g, 0.799 mmol, Preparation #E.1.2) in chloroform (20 mL) was added iodobenzene diacetate (0.343 g, 1.06 mmol) in one portion. The mixture was allowed to warm to RT and stirred for about another 1 h. The reaction mixture was quenched with water (20 mL) and the product was extracted with chloroform (2×20 mL). The organic layer was washed with water (2×15 mL), dried over sodium sulphate and evaporated to dryness. The residue obtained was purified by column chromatography using silica gel (60-120 mesh) eluting with 50% n-hexane and EtOAc. Relevant fractions containing the required compound were combined and evaporated to dryness under reduced pressure to afford tert-butyl 4-(3-(6-(4-methoxybenzylcarbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)piperidine-1-carboxylate 0.1 g (29%). MS m/z: 510 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with water (20 mL)
  2. extractionthe product was extracted with chloroform (2×20 mL)
  3. washThe organic layer was washed with water (2×15 mL)
  4. dry with materialdried over sodium sulphate
  5. customevaporated to dryness
  6. customThe residue obtained
  7. customwas purified by column chromatography
  8. washeluting with 50% n-hexane and EtOAc
  9. additionRelevant fractions containing the required compound
  10. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-9ecf60a6f24c4c8da7a1f8662144c15f
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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