Acetic Acid → Hnifedipine

HRID 894723Notes

Reaction equation

HRID 894723 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH:25]=[O:26])=[C:5]([C:21]([O:23][CH3:24])=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])[C:7]=1[C:8]([O:10][CH3:11])=[O:9].[BH4-].[Na+].C(O)(=O)C>CO>[CH3:1][C:2]1[NH:3][C:4]([CH2:25][OH:26])=[C:5]([C:21]([O:23][CH3:24])=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])[C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4311764Sodium borohydrideHCID 15737325Dimethyl 2-methyl-4-(2-nitrophenyl)-6-formyl-1,4-dihydropyridine-3,5-dicarboxylate

Product 1

HCID 12896956HnifedipineYield 21.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of dimethyl 2-methyl-4-(2-nitrophenyl)-6-formyl-1,4-dihydropyridine-3,5-dicarboxylate (3.60 g) in methanol (72 ml) was cooled at 0° C., and sodium borohydride (0.2271 g) was added bit by bit thereto under cooling with stirring. The mixture was stirred at the same temperature for 15 minutes. The reaction mixture was adjusted to about pH 6 with 50% acetic acid and the methanol was distilled off under reduced pressure below 30° C. The residual solution was diluted with water (100 ml) and extracted with ethyl acetate. The extract was washed with water, an aqueous sodium bicarbonate solution and water in turn, dried over magnesium sulfate and then evaporated to dryness. The residual oil (3.70 g) was crystallized by triturating with diisopropyl ether to give crude crystals (2.74 g), which were recrystallized in first from methanol (8 ml) and then from ethyl acetate (10 ml) to give pure crystals of dimethyl 2-methyl-4-(2-nitrophenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate (770 mg), mp 164.5 to 165° C. The whole mother liquor of above recrystallizations were combined together and concentrated. The crystalline residue was collected by filtration and washed with methanol (5 ml) to give additional crystals (1.72 g), which were recrystallized from ethyl acetate to give additional pure specimen of the same product obtained above, (840 mg) m.p. 164.5° to 165° C. Total yield, 1.61 g.

Workup

  1. temperatureunder cooling
  2. stirringThe mixture was stirred at the same temperature for 15 minutes
  3. distillationthe methanol was distilled off under reduced pressure below 30° C
  4. additionThe residual solution was diluted with water (100 ml)
  5. extractionextracted with ethyl acetate
  6. washThe extract was washed with water
  7. dry with materialan aqueous sodium bicarbonate solution and water in turn, dried over magnesium sulfate
  8. customevaporated to dryness
  9. customThe residual oil (3.70 g) was crystallized
  10. customby triturating with diisopropyl ether
  11. customto give crude crystals (2.74 g), which
  12. customwere recrystallized in first from methanol (8 ml)

Sources & evidence

ORD record
ord-2975050046ec44f68da5cf7226be12aa
Source dataset
uspto-grants-1981_08
Patent number
US04284634

Reaction notes

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