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

HRID 8777

Reaction equation

HRID 8777 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 4-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 room temperature 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 room temperature 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-e31142420d854a6b93bb0fdda233b4cb
Source dataset
uspto-grants-2006_08
Patent number
US07091211B2

Linked notes

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