Phenol → HCID 72465994, compound

HRID 853647Notes

Reaction equation

HRID 853647 reaction equation
[CH2:1]([O:8][CH2:9][P:10](=[O:13])([OH:12])[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.N1C=NN=N1.[C:23]1(O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C.[C:37]([O:42][CH2:43][CH3:44])(=[O:41])[CH:38]([CH3:40])O>CC#N.C1(C)C=CC=CC=1>[CH2:43]([O:42][C:37](=[O:41])[CH:38]([O:13][P:10]([CH2:9][O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([O:12][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:11])[CH3:40])[CH3:44]

Participants

9

Reactant 6

HCID 996PhenolHCID 7344Ethyl LactateHCID 8471Triethylamine2×HCID 24386Thionyl ChlorideHCID 58928780HCID 58928780, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 72465994HCID 72465994, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent3×HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of benzyloxymethyl phosphonic acid (520 mg, 2.57 mmol) in CH3CN (5 mL) was added thionyl chloride (0.75 mL, 10.3 mmol) and heated to 70° C. in an oil bath. After the reaction mixture was stirred for 2 h at 70° C., the mixture was concentrated and azeotroped with toluene. To a solution of the crude chloridate in toluene (5 mL) was added tetrazole (18 mg, 0.26 mmol) at 0° C. To this mixture was added phenol (121 mg, 1.28 mmol) and triethylamine (0.18 mL, 1.28 mmol) in toluene (3 mL) at 0° C. After the reaction mixture was warmed to room temperature and stirred for 2 h, ethyl lactate (0.29 mL, 2.57 mmol) and triethylamine (0.36 mL, 2.57 mmol) in toluene (2.5 mL) were added. The reaction mixture was stirred for 16 hours at room temperature, at which time the mixture was partitioned between EtOAc and sat. NH4Cl. The organic phase was washed with sat. NH4Cl, 1M NaHCO3, and brine, then dried over Na2SO4, filtered, and evaporated under reduced pressure. The crude product was chromatographed on silica gel (eluting 20-40% EtOAc/hexane) to give two diastereomers (isomer A and isomer B) of 2-(benzyloxymethyl-phenoxy-phosphinoyloxy)-propionic acid ethyl ester 196 (66 mg, 109 mg, 18% total) as colorless oils.

Workup

  1. concentrationthe mixture was concentrated
  2. customazeotroped with toluene
  3. temperatureAfter the reaction mixture was warmed to room temperature
  4. stirringstirred for 2 h
  5. stirringThe reaction mixture was stirred for 16 hours at room temperature, at which time the mixture
  6. customwas partitioned between EtOAc and sat. NH4Cl
  7. washThe organic phase was washed with sat. NH4Cl, 1M NaHCO3, and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe crude product was chromatographed on silica gel (eluting 20-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-7d32a0083990467da9d0f6f1bd64a6d9
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

Loading…