Acetic Acid → (R)-methyl 1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxylate

HRID 1801588Notes

Reaction equation

HRID 1801588 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:11][CH2:10]2)=[C:5]([NH:19][C:20]([C:22]2[CH:26]=[C:25]([CH3:27])[O:24][N:23]=2)=[O:21])[CH:4]=1)=O.C(O)(=O)C.[C:32]1([C@H:38]([NH2:40])[CH3:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CCOC(C)=O>[CH3:27][C:25]1[O:24][N:23]=[C:22]([C:20]([NH:19][C:5]2[CH:4]=[C:3]([CH2:1][NH:40][C@@H:38]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH3:39])[CH:8]=[CH:7][C:6]=2[N:9]2[CH2:14][CH2:13][CH:12]([C:15]([O:17][CH3:18])=[O:16])[CH2:11][CH2:10]2)=[O:21])[CH:26]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6431891-Phenethylamine, (+)-HCID 5049666Sodium triacetoxyborohydrideHCID 59803206Methyl 1-(4-formyl-2-(5-methylisoxazole-3-carboxamido)phenyl)piperidine-4-carboxylate

Product 1

HCID 59803195(R)-methyl 1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxylateYield 67%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 1-(4-formyl-2-(5-methylisoxazole-3-carboxamido)phenyl)piperidine-4-carboxylate 60 (0.268 g, 0.72 mmol) in DCE (10 mL) was added acetic acid (0.045 mL, 0.78 mmol), (R)-1-phenylethanamine (0.11 mL, 0.88 mmol), and NaBH(OAc)3 (0.186 g, 0.88 mmol). The reaction mixture was stirred at room temperature for 15 h and diluted with EtOAc. The organic phase was washed with saturated NaHCO3 (1×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 70% to 100% EtOAc in hexanes) gave (R)-methyl 1-(2-(5-methylisoxazole-3-carboxamido)-4-((1-phenylethylamino)methyl)phenyl)piperidine-4-carboxylate 61 (0.230 g, 67% yield) as a white solid. Mass spectrum: calculated for C27H32N4O4 476.2. found 477.3 (M++1).

Workup

  1. washThe organic phase was washed with saturated NaHCO3 (1×), brine (1×)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by flash column chromatography on silica gel (eluted with 70% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6a8cf28e57464ec49a91e18dd76facfa
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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