p-Toluenesulfonic acid → (R)-1-tert-butyl 3-ethyl 4-(1-phenylethylamino)-5,6-dihydropyridine-1,3(2H)-dicarboxylate

HRID 2261047Notes

Reaction equation

HRID 2261047 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH:3]1[C:15]([O:17][CH2:18][CH3:19])=[O:16].[C:20]1([C@H:26]([NH2:28])[CH3:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:20]1([C@H:26]([NH:28][C:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C:3]=2[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 6431891-Phenethylamine, (+)-HCID 64208761-(1,1-Dimethylethyl) 3-ethyl 4-oxo-1,3-piperidinedicarboxylate

Product 1

HCID 10872460(R)-1-tert-butyl 3-ethyl 4-(1-phenylethylamino)-5,6-dihydropyridine-1,3(2H)-dicarboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 252A (22 g, 81 mmol) and toluene (400 mL) was treated with (R)-1-phenylethanamine (12.5 mL, 97 mmol) and p-TsOH (1.5 g). The reaction mixture was heated to reflux with a Dean-Stark trap for 23 hours. The mixture was cooled to room temperature, washed with saturated aqueous NaHCO3 (2×200 mL) and brine (2×200 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude material was filtered through a pad of silica (100% CH2Cl2) and concentrated to provide 14.7 g (yield: 49%) of Compound 252B as an oil.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux with a Dean-Stark trap for 23 hours
  3. washwashed with saturated aqueous NaHCO3 (2×200 mL) and brine (2×200 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. filtrationThe crude material was filtered through a pad of silica (100% CH2Cl2)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9600fe591d2b4c4bbfb486bed81e5c19
Source dataset
uspto-grants-2010_12
Patent number
US07846931B2

Reaction notes

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