Triethylamine → HCID 9948873, compound

HRID 991025Notes

Reaction equation

HRID 991025 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][C:10]([CH3:21])([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11](O)=[O:12])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.Cl.[NH2:29][OH:30].C(N(CC)CC)C>CN(C=O)C.C(Cl)Cl.C1COCC1.O>[OH:30][NH:29][C:11](=[O:12])[C:10]([S:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)([CH3:21])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chloride2×HCID 443297Hydroxyamine hydrochlorideHCID 15484979HCID 15484979, compound

Product 1

HCID 9948873HCID 9948873, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

2-(4-methoxy-phenylsulfanyl)-2-methyl-3-phenyl-propionic acid ethyl ester (4.12 g, 12 mmol) dissolved in methanol (50 ml) and 10 N NaOH (20 ml) was added. The reaction was allowed to stir overnight at room temperature. The reaction mixture was concentrated, diluted with 1:1 hexane:diethyl ether and extracted with H2O. The water layer was cooled with ice and acidified to pH 3. The acid was then extracted with chloroform and the organic layer was dried over MgSO4, filtered and concentrated to afford of 2-(4-methoxy-phenylsulfanyl)-2-methyl-3-phenyl-propionic acid as a low melting solid. Yield 580 mg, 16%; MS: 303.2 (M+H)+. To a stirred solution of 2-(4-methoxy-phenylsulfanyl)-2-methyl-3-phenyl-propionic acid (0.5 g, 1.65 mmol) and DMF (2 drops) in CH2Cl2 (100 ml) at 0° C., oxalyl chloride (1.0 gm, 8 mmol) was added in a drop-wise manner. After the addition, the reaction mixture was stirred at room temperature for 1 hour. Simultaneously, in a separate flask a mixture of hydroxylamine hydrochloride (2.0 gm, 29 mmol) and triethylamine (5 ml, excess) was stirred in THF:water (5:1, 30 ml) at 0° C. for 1 hour. At the end of 1 hour, the oxalyl chloride reaction mixture was concentrated and the pale yellow residue was dissolved in 10 ml of CH2Cl2 and added slowly to the hydroxylamine at OC. The reaction mixture was stirred at room temperature for 24 hours and concentrated. The residue obtained was extracted with chloroform and washed well with water. The product obtained was purified by silica gel column chromatography and eluted with ethyl acetate. The N-hydroxy-2-(4-methoxyphenylsulfanyl)-2-methyl-3-phenyl -propionamide was isolated as a colorless solid. mp 88° C.; Yield, 300 mg, 57%; MS: 318 (M+H)+; 1H NMR (300 Mz, CDCl3): δ 1.32 (s, 3H), 3.07 (d, J=11 Hz, 1H), 3.23 (d, J=11 Hz, 1H), 3.79 (s, 3H), 6.83-7.36 (m, 9H).

Workup

  1. additionAfter the addition
  2. concentrationwas concentrated
  3. dissolutionthe pale yellow residue was dissolved in 10 ml of CH2Cl2
  4. additionadded slowly to the hydroxylamine at OC
  5. stirringThe reaction mixture was stirred at room temperature for 24 hours
  6. concentrationconcentrated
  7. customThe residue obtained
  8. extractionwas extracted with chloroform
  9. washwashed well with water
  10. customThe product obtained
  11. customwas purified by silica gel column chromatography
  12. washeluted with ethyl acetate

Sources & evidence

ORD record
ord-1387a93e3815445082b577db2c13a8cb
Source dataset
uspto-grants-2002_10
Patent number
US06462073B2

Reaction notes

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