Thionyl Chloride → (+)-4,5-dihydro-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-3-phenyl-1H-pyrazole-5-carboxylic acid, phenylmethyl ester

HRID 1757940Notes

Reaction equation

HRID 1757940 reaction equation
[OH:1][P:2]([CH2:14][C:15]([OH:17])=O)([CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:3].S(Cl)(Cl)=O.Cl.[C:23]1([C:29]2[CH2:33][CH:32]([C:34]([O:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[O:35])[NH:31][N:30]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.ClC(OC(=O)C(C)(C)C)C(OCC)=O>C(N(CC)CC)C.ClCCl.CN(C)C=O>[OH:1][P:2]([CH2:14][C:15]([N:31]1[CH:32]([C:34]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:35])[CH2:33][C:29]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:30]1)=[O:17])([CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:3]

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 13102401((4-Phenylbutyl)hydroxyphosphoryl)acetic acid2×HCID 13102402Ethyl 2-chloro-2-pivaloyloxyacetateHCID 131712948HCID 131712948, compound

Product 1

HCID 86738774(+)-4,5-dihydro-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-3-phenyl-1H-pyrazole-5-carboxylic acid, phenylmethyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A solution of 10 g. of [hydroxy(4-phenylbutyl)phosphinyl]acetic acid, from part (b), in 40 ml. of dry dichloromethane containing 0.2 ml. of dimethylformamide is heated to reflux temperature. Thionyl chloride (5.1 g.) is added dropwise while maintaining the temperature at reflux. After an additional 30 minutes heating, the solution is cooled to 5° and a solution of 11.6 g. of (+)-4,5-dihydro-3-phenyl-1H-pyrazole-5-carboxylic acid, phenylmethyl ester, hydrochloride (1:1), from part (a), in 50 ml. of dichloromethane is added at once, followed by dropwise addition of 11.9 g. of triethylamine while the temperature is maintained at 5°-10° with cooling. After stirring overnight at ambient temperature, the mixture is washed three times with aqueous hydrochloric acid (1.5 N) and three times with water. The organic solution is dried (MgSO4) and concentrated in vacuo to give (+)-4,5-dihydro-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-3-phenyl-1H-pyrazole-5-carboxylic acid, phenylmethyl ester which can be crystallized from acetone.

Workup

  1. temperatureto reflux temperature
  2. temperaturewhile maintaining the temperature
  3. temperatureat reflux
  4. temperatureAfter an additional 30 minutes heating
  5. temperaturethe solution is cooled to 5°
  6. additionfollowed by dropwise addition of 11.9 g
  7. temperaturewith cooling
  8. washthe mixture is washed three times with aqueous hydrochloric acid (1.5 N) and three times with water
  9. dry with materialThe organic solution is dried (MgSO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f4301a53468d4adb8c4fabee82167e4d
Source dataset
uspto-grants-1983_02
Patent number
US04371526

Reaction notes

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