Phenylacetaldehyde → 2-Phenyl-1-(thiophene-2-sulfonylamino)-ethyl-phosphonic Acid Diethyl Ester

HRID 1816216Notes

Reaction equation

HRID 1816216 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([NH2:9])(=[O:8])=[O:7].[P:10]([O-:17])([O:14][CH2:15][CH3:16])[O:11][CH2:12][CH3:13].[C:18]1([CH2:24][CH:25]=O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(Cl)(=O)C>[CH2:12]([O:11][P:10]([CH:25]([NH:9][S:6]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)(=[O:8])=[O:7])[CH2:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:17])[O:14][CH2:15][CH3:16])[CH3:13]

Participants

5

Reactant 3

HCID 998PhenylacetaldehydeHCID 728812-ThiophenesulfonamideHCID 3780918Diethylphosphite

Product 1

HCID 228909322-Phenyl-1-(thiophene-2-sulfonylamino)-ethyl-phosphonic Acid Diethyl EsterYield 349.4%

Reagents, catalysts & solvents 1

HCID 6367Acetyl chlorideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of sulfonamide (vi) (500 mg; 0.31 mmol) in acetyl chloride (5 mL) was slowly added diethyl phosphite (400 μL; 0.31 mmol). The reaction was cooled to 0° C. and then phenylacetaldehyde (450 μL; 0.39 mmol) was added dropwise. The reaction was gradually warmed to ambient temperature and after 6 hrs the homogeneous solution was concentrated. The residue was diluted with dichloromethane (25 mL) then washed successively with water (10 mL), saturated sodium bicarbonate (10 mL) and brine (10 mL). The combined organic extracts wre dried (MgSO4), evaporated and initially purified by flash chromatography (ethyl acetate-hexanes; 3:2). A second purification by flash chromatography (acetone-hexanes; 3:7) yielded diethyl phosphonate (xii) (437 mg, 35%) as a colorless solid; 1H NMR (400 MHz, CDCl3) δH 1.22 (t, J=7 Hz, 3 H, OCH2CH3), 1.26 (t, J=7 Hz, 3 H, OCH2CH3), 2.89 (dt, J=8, 14 Hz, 1 H, CHPh), 3.12 (dt, J=6, 14 Hz, 1 H, CHPh), 3.96-4.23 (m, 5 H, NCHP and OCH2CH3), 6.38 (dd, J=2, 9.5 Hz, 1 H, NH), 6.92-6.93 (m, 1 H, Ar—H), 7.12-7.20 (m, 5 H, Ar—H), 7.33-7.34 (m, 1 H, Ar—H), 7.43-7.45 (m, 1 H, Ar—H).

Workup

  1. temperatureThe reaction was gradually warmed to ambient temperature and after 6 hrs the homogeneous solution
  2. concentrationwas concentrated
  3. additionThe residue was diluted with dichloromethane (25 mL)
  4. washthen washed successively with water (10 mL), saturated sodium bicarbonate (10 mL) and brine (10 mL)
  5. dry with materialThe combined organic extracts wre dried (MgSO4)
  6. customevaporated
  7. custominitially purified by flash chromatography (ethyl acetate-hexanes; 3:2)
  8. customA second purification by flash chromatography (acetone-hexanes; 3:7)

Sources & evidence

ORD record
ord-d314ba0277354638becdbac5ea7fc9ff
Source dataset
uspto-grants-2005_04
Patent number
US06884791B2

Reaction notes

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