Benzyl Alcohol → (+/-)-2-[[Phenylmethoxy(4-phenylbutyl)phosphinyl]oxy]propionic acid, ethyl ester

HRID 256326Notes

Reaction equation

HRID 256326 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][P:11](=[O:14])([OH:13])[OH:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)(Cl)(Cl)Cl.C(N(CC)CC)C.[C:28]([O:33][CH2:34][CH3:35])(=[O:32])[CH:29]([CH3:31])O.[CH2:36](O)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C(Cl)Cl.C1C=CC=CC=1>[C:37]1([CH2:36][O:14][P:11]([CH2:10][CH2:9][CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([O:13][CH:29]([CH3:31])[C:28]([O:33][CH2:34][CH3:35])=[O:32])=[O:12])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

8

Reactant 5

HCID 244Benzyl AlcoholHCID 7344Ethyl LactateHCID 8471TriethylamineHCID 24819Phosphorus pentachlorideHCID 13687984(4-Phenylbutyl)phosphonic acid

Product 1

HCID 86739440(+/-)-2-[[Phenylmethoxy(4-phenylbutyl)phosphinyl]oxy]propionic acid, ethyl esterYield 60%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-phenylbutyl phosphonic acid from Part A (0.70 g, 3.27 mmole), benzene (10 ml), and PCl5 (1.36 g, 6.54 mmole) was refluxed under argon for 30 minutes. The benzene and POCl3 were removed in vacuo and the residue taken up in CH2Cl2 (5 ml). After cooling to 0° C. (ice-bath), triethylamine (1.3 ml, 9.39 mmole) was added followed by dropwise treatment with d,l ethyl lactate (0.39 ml, 3.3 mmole) in CH2Cl2 (3 ml) over a 5 minute period. After 1 hour benzyl alcohol (0.35 ml, 3.3 mmole) in CH2Cl2 (3 ml) was added dropwise over 2 minutes, the ice-bath removed, and the reaction mixture allowed to stir for 2 hours. The reaction mixture was diluted with EtOAc then washed with H2O, 5% KHSO4, saturated NaHCO3, brine, dried (MgSO4 ), and evaporated. The residue (1.3 g) was chromatographed on silica (70 g) eluting with 2/1 hexane/EtOAc to obtain the title compound (0.80 g, 1.98 mmole; 60% yield) as an oil.

Workup

  1. temperaturewas refluxed under argon for 30 minutes
  2. customThe benzene and POCl3 were removed in vacuo
  3. additionwas added
  4. customthe ice-bath removed
  5. additionThe reaction mixture was diluted with EtOAc
  6. washthen washed with H2O, 5% KHSO4, saturated NaHCO3, brine
  7. dry with materialdried (MgSO4 )
  8. customevaporated
  9. customThe residue (1.3 g) was chromatographed on silica (70 g)
  10. washeluting with 2/1 hexane/EtOAc

Sources & evidence

ORD record
ord-7cbdb644b60344d4abbc460b61c07351
Source dataset
uspto-grants-1987_10
Patent number
US04703043

Reaction notes

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