Sodium hydride → 2-(Diethoxyphosphoryl)-3-cyclopropylproprionic acid 4-methoxybenzyl ester

HRID 2303686

Reaction equation

HRID 2303686 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:23]=[CH:22][C:8]([CH2:9][O:10][C:11](=[O:21])[CH2:12][P:13]([O:18][CH2:19][CH3:20])([O:15][CH2:16][CH3:17])=[O:14])=[CH:7][CH:6]=1.Br[CH2:25][CH:26]1[CH2:28][CH2:27]1.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)C>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:9][O:10][C:11](=[O:21])[CH:12]([P:13]([O:15][CH2:16][CH3:17])([O:18][CH2:19][CH3:20])=[O:14])[CH2:25][CH:26]2[CH2:28][CH2:27]2)=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 516892Sodium BicarbonateHCID 540209272-(Diethoxyphosphoryl)acetic acid para-methoxybenzyl ester

Product 1

HCID 540841052-(Diethoxyphosphoryl)-3-cyclopropylproprionic acid 4-methoxybenzyl esterYield 60.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of 60% sodium hydride in mineral oil (0.840 g, 21.0 mmol) in DMF (100 mL) was added a solution of 2-(diethoxyphosphoryl)acetic acid para-methoxybenzyl ester (6.04 g, 19.1 mmol) from Step A in DMF (10 mL). The reaction mixture was stirred for 30 min at room temperature. Bromomethylcyclopropane (2.4 mL, 24.8 mmol) was added and the reaction mixture was stirred at rt for 12 h. The reaction mixture was diluted with diethyl ether, poured into saturated sodium bicarbonate, and extracted three times with diethyl ether. The organic layers were combined, washed with saturated sodium chloride, dried over sodium sulfate, and filtered. The volatiles were removed in vacuo and the residue was purified by FC (40% ethyl acetate in hexanes) to afford 4.31 g of the title compound.

Workup

  1. stirringthe reaction mixture was stirred at rt for 12 h
  2. extractionextracted three times with diethyl ether
  3. washwashed with saturated sodium chloride
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customThe volatiles were removed in vacuo
  7. customthe residue was purified by FC (40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5fbe0a5fb4fc4a60bad773b49e34a777
Source dataset
uspto-grants-2002_08
Patent number
US06432981B1

Linked notes

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