Diethyl Ether → 3-methyl 1-(phenylmethyl) 4-[3-chloro-4-(trifluoromethyl)phenyl]-5,6-dihydro-1,3(2H)-pyridinedicarboxylate

HRID 639852Notes

Reaction equation

HRID 639852 reaction equation
FC(F)(F)S(O[CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:9][CH:8]1[C:23]([O:25][CH3:26])=[O:24])(=O)=O.[Cl:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][C:35]=1[C:36]([F:39])([F:38])[F:37].C([O-])([O-])=O.[Na+].[Na+].CCOCC>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:29][C:30]1[CH:31]=[C:32]([C:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[O:14])[CH2:9][C:8]=2[C:23]([O:25][CH3:26])=[O:24])[CH:33]=[CH:34][C:35]=1[C:36]([F:37])([F:38])[F:39]

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 10340Sodium CarbonateHCID 37729583-Chloro-4-(trifluoromethyl)benzeneboronic acidHCID 866201973-Methyl 1-(phenylmethyl) 4-{[(trifluoromethyl)sulfonyl]oxy}-1,3-piperidinedicarboxylate

Product 1

HCID 592560273-methyl 1-(phenylmethyl) 4-[3-chloro-4-(trifluoromethyl)phenyl]-5,6-dihydro-1,3(2H)-pyridinedicarboxylateYield 94.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 3-methyl 1-(phenylmethyl) 4-{[(trifluoromethyl)sulfonyl]oxy}-1,3-piperidinedicarboxylate (3 g) (P38) and [3-chloro-4-(trifluoromethyl)phenyl]boronic acid (1.826 g) in dry toluene (37 mL) under N2 atmosphere at 0° C., Pd(PPh3)4 (292 mg) dissolved in absolute EtOH (26 ml), was added followed by Na2CO3 2M (21 mL). The reaction mixture was heated to 80° C. for 2 h. Et2O was then added to the solution and the organic phase was separated. The aqueous layer was extracted with Et2O and the combined organic phases were washed with saturated NaCl aqueous solution, dried and concentrated under vacuum. The crude was purified by flash-chromatography (eluting with cyclohexane/ethyl acetate from 9:1 to 8:2) to give the title compound (3.03 g).

Workup

  1. additionwas added
  2. customthe organic phase was separated
  3. extractionThe aqueous layer was extracted with Et2O
  4. washthe combined organic phases were washed with saturated NaCl aqueous solution
  5. customdried
  6. concentrationconcentrated under vacuum
  7. customThe crude was purified by flash-chromatography (eluting with cyclohexane/ethyl acetate from 9:1 to 8:2)

Sources & evidence

ORD record
ord-8d03fd01c2df4146a943d123b6f4b349
Source dataset
uspto-grants-2010_04
Patent number
US07691893B2

Reaction notes

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