Ammonium Chloride → [3-(4-Fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester

HRID 1267458Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][C:3]=1[CH3:10].[CH2:11]([O:13][P:14]([CH2:19][CH:20]1[CH2:22][O:21]1)(=[O:18])[O:15][CH2:16][CH3:17])[CH3:12].[Cl-].[NH4+]>C1COCC1>[CH2:16]([O:15][P:14]([CH2:19][CH:20]([OH:21])[CH2:22][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([CH3:10])[CH:4]=1)(=[O:18])[O:13][CH2:11][CH3:12])[CH3:17]

Participants

Conditions

Temperature: -15 °C

Procedure

To a solution of 4-fluoro-3-methylphenylmagnesium bromide (0.5M in Et2O, 15.5 mL, 7.75 mmol) in THF (10 mL) at −30° C. was added Cul (196 mg, 1.03 mmol) and the reaction mixture was stirred for 10 minutes. The reaction mixture was warmed to −15° C. and oxiranylmethyl-phosphonic acid diethyl ester (1 g, 5.2 mmol) in THF (10 mL) was added. The reaction mixture was stirred at 0° C. for 2 h. Saturated aqueous ammonium chloride was added and the product was extracted into EtOAc. The organic solution was dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes) provided [3-(4-fluoro-3-methyl-phenyl)-2-hydroxy-propyl]-phosphonic acid diethyl ester (1.37 g).

Workup

stirringThe reaction mixture was stirred at 0° C. for 2 h
extractionthe product was extracted into EtOAc
dry with materialThe organic solution was dried (MgSO4)
filtrationfiltered
concentrationconcentrated
customPurification by medium pressure chromatography (20% EtOAc in hexanes to 70% EtOAc in hexanes)

Sources & evidence

ORD record: ord-b138276da03140a38785eb67875bd10e
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06552067B2

Reaction notes

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