Ammonium Chloride → Diisopropyl-4-(4-bromobenzyl)-1-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonate

HRID 477049Notes

Reaction equation

HRID 477049 reaction equation
[CH:1]([O:4][P:5]([CH:11]1[CH:16]=[CH:15][N:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:13]=[CH:12]1)(=[O:10])[O:6][CH:7]([CH3:9])[CH3:8])([CH3:3])[CH3:2].C(=O)=O.CC(C)=O.C([Li])CCC.[Br:34][C:35]1[CH:42]=[CH:41][C:38]([CH2:39]Br)=[CH:37][CH:36]=1.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[CH:7]([O:6][P:5]([C:11]1([CH2:39][C:38]2[CH:41]=[CH:42][C:35]([Br:34])=[CH:36][CH:37]=2)[CH:12]=[CH:13][N:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:15]=[CH:16]1)(=[O:10])[O:4][CH:1]([CH3:2])[CH3:3])([CH3:9])[CH3:8]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 685274-Bromobenzyl bromideHCID 11652617Diisopropyl-1-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonateHCID 18522661Acetone cardiceHCID 178418339Butyllithium2×

Product 1

HCID 86743573Diisopropyl-4-(4-bromobenzyl)-1-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonateYield 60%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

3.0 g of diisopropyl-1-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonate was dissolved in 50 ml of tetrahydrofuran. The solution was cooled to -78° C. with a dry ice-acetone freezing mixture. In a stream of nitrogen, 6.8 ml of a hexane solution of n-butyllithium was slowly added dropwise. A solution of 2.50 g of p-bromobenzyl bromide in 10 ml of tetrahydrofuran was added dropwise. The temperature of the solution was returned to room temperature, and the solution was stirred for 20 hours. The excess of n-butyllithium was decomposed with ammonium chloride, and the solvent was evaporated. The residue was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium hydrogen carbonate, a saturated aqueous solution of sodium thiosulfate and a saturated aqueous solution of sodium chloride in this order, and the solvent was evaporated. The residue was subjected to silica gel column chromatography. The column was eluted with a 1:9 mixture of acetone and benzene to give 2.76 g (yield 56.6%) of diisopropyl-4-(4-bromobenzyl)-1-ethoxycarbonyl-1,4-dihydropyridine-4-phosphonate as a brown oil.

Workup

  1. customwas returned to room temperature
  2. customthe solvent was evaporated
  3. extractionThe residue was extracted with ethyl acetate
  4. washThe extract was washed with a saturated aqueous solution of sodium hydrogen carbonate
  5. customa saturated aqueous solution of sodium thiosulfate and a saturated aqueous solution of sodium chloride in this order, and the solvent was evaporated
  6. washThe column was eluted with a 1:9 mixture of acetone and benzene

Sources & evidence

ORD record
ord-8c25b7c95574462b99287dc3b588fdf0
Source dataset
uspto-grants-1989_12
Patent number
US04886822

Reaction notes

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