HCID 10907345, compound → (4R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

HRID 962922Notes

Reaction equation

HRID 962922 reaction equation
[CH3:1][C:2]1[NH:3][C:4]([CH3:37])=[C:5]([C:34]([OH:36])=[O:35])[C@@H:6]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([N+:31]([O-:33])=[O:32])[CH:26]=2)[C:7]=1[C:8]([O:10][CH2:11]CNC(=O)C1C=CC=CC=1C(O)=O)=[O:9].C[O-].[Na+]>O>[CH3:1][C:2]1[NH:3][C:4]([CH3:37])=[C:5]([C:34]([OH:36])=[O:35])[C@@H:6]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([N+:31]([O-:33])=[O:32])[CH:26]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Participants

4

Reactant 2

HCID 10907345HCID 10907345, compoundHCID 10942334Sodium Methoxide

Product 1

HCID 748472(4R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acidYield 67.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To 50 mg of the (4R)-1,4-dihydro-2,6-dimethyl-3-[2(2-carboxybenzoyl) aminoethyl]oxycarbonyl-4-(3-nitrophenyl)pyridine-5-carboxylic acid obtained in Example 8 was added 5 ml of sodium methoxide (28% methanol solution) and the mixture was stirred at 50° C. for 2 hours. After it was diluted with 10 ml of water, the reaction mixture was washed with 5 ml of ethyl acetate and the aqueous layer was adjusted to pH 3 before it was extracted 3 times with 10 ml each of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and evaporated to dryness. The yellow substance thus obtained was purified on a column packed with 120 ml of Sephadex LH-20 (solvent: methanol) to obtain 22 mg of (4R)-1,4-dihydro-2,6-dimethyl-3-methyloxycarbonyl-4-(3-nitrophenyl) pyridine-5-carboxylic acid. The optical purity of this substance was analyzed by HPLC (mobile phase: hexane:ethanol:acetic acid=90:10:0.1, flow rate: 1.0 ml/minute, detection UV 254 nm) using an otical resolution column: CHIRALPAK AS (4.6 mm ×250 mm) manufactured by Daicel Chemical Industries Ltd. As a result, it revealed that the optical purity of the substance was 100% and the retention time was 12.5 minutes. 1 H-NMR(CD3OD): δ 8.09(1 H,s), 7.99(1 H,d,J=9.5 Hz), 7.65(1 H,d,J=7.7 Hz), 7.44(1 H,t,j=8.1 Hz), 5.09(1 H,s), 3.62(3 H,S), 2.34(3 H, s), 2.33(3 H,s)

Workup

  1. washthe reaction mixture was washed with 5 ml of ethyl acetate
  2. extractionwas extracted 3 times with 10 ml each of ethyl acetate
  3. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  4. customevaporated to dryness
  5. customThe yellow substance thus obtained
  6. customwas purified on a column

Sources & evidence

ORD record
ord-ac22f523d3764bb482bfa667bdfa7071
Source dataset
uspto-grants-1998_06
Patent number
US05760238

Reaction notes

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