Water → HCID 10808872, compound

HRID 327160Notes

Reaction equation

HRID 327160 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3]([OH:8])([CH3:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([S:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:18]([C:29]#[N:30])[CH:17]=1.O>CN(C)C(=O)C>[C:23]1([S:22][C:19]2[CH:20]=[CH:21][C:16]([NH:15][C:4](=[O:5])[C:3]([OH:8])([CH3:7])[C:2]([F:10])([F:9])[F:1])=[CH:17][C:18]=2[C:29]#[N:30])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl ChlorideHCID 1471779HCID 1471779, compoundHCID 27751253,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid

Product 1

HCID 10808872HCID 10808872, compoundYield 158.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred, cooled (-20° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (2.16 g 13.7 mmol) in N,N-dimethylacetamide (20 mL) was rapidly added thionyl chloride (1.73 g, 14.5 mmol) and the mixture (a precipitate formed after a few minutes) stirred at -20° C. to -10° C. for 1 hour. (4-Amino-2-cyanophenyl)phenyl sulfide (2.08 g, 9.2 mmol) was then added in one portion and the mixture allowed to stir at room temperature overnight. The solution was poured into 500 mL of water and extracted with two 100 mL portions of ethyl ether. The oil obtained-on removal of the ethyl ether was chromatographed on 325 g of silica gel using an ethyl ether (0%, 5%, 10% and 20%) in methylene chloride gradient. The proper fractions were combined, the solvent removed in vacuo and the residue heated overnight at 60° C./0.1 mm to yield 5.35 g (93%) of N-(4-phenylthio-3-cyanophenyl)-3,3,3,-trifluoro-2-hydroxy-2-methylpropanamide, mp 124°-126° C. 1H--NMR (300 MHz, d6 --DMSO): 1.59 (s, 3H, CH3), 7.32-7.47 (m, 6H, aromatic), 7.59 (s, 1H, OH), 8.07 (dd 1H, J=8.8, 2.3 Hz, aromatic), 8.33 (d, 1H, J=2.3 Hz, aromatic), 10.48 (s, 1H, NH). MS (CI, CH4): 367(M+1).

Workup

  1. customthe mixture (a precipitate formed after a few minutes)
  2. stirringto stir at room temperature overnight
  3. extractionextracted with two 100 mL portions of ethyl ether
  4. customThe oil obtained-on removal of the ethyl ether
  5. customwas chromatographed on 325 g of silica gel using an ethyl ether (0%, 5%, 10% and 20%) in methylene chloride gradient
  6. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-a6a3996b7f864782824910e67a166cee
Source dataset
uspto-grants-1993_12
Patent number
US05272163

Reaction notes

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