Dimethylformamide → HCID 59714672, compound

HRID 547579Notes

Reaction equation

HRID 547579 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[S:27]1[CH2:32][CH2:31][CH:30]([CH2:33][NH:34][C@@H:35]([C:37]2[N:38]([C:48]3[CH:53]=[CH:52][C:51]([O:54][CH2:55][C:56]([F:59])([F:58])[F:57])=[CH:50][CH:49]=3)[C:39](=[O:47])[C:40]3[CH:46]=[CH:45][CH:44]=[N:43][C:41]=3[N:42]=2)[CH3:36])[CH2:29][CH2:28]1.C(N(CC)CC)C>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:34]([C@@H:35]([C:37]2[N:38]([C:48]3[CH:49]=[CH:50][C:51]([O:54][CH2:55][C:56]([F:57])([F:59])[F:58])=[CH:52][CH:53]=3)[C:39](=[O:47])[C:40]3[CH:46]=[CH:45][CH:44]=[N:43][C:41]=3[N:42]=2)[CH3:36])[CH2:33][CH:30]2[CH2:31][CH2:32][S:27][CH2:28][CH2:29]2)=[O:11])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27375934-Fluoro-3-(trifluoromethyl)phenylacetic acidHCID 58617372HCID 58617372, compound

Product 1

HCID 59714672HCID 59714672, compoundYield 90.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

The compound 4-fluoro-3-trifluoromethylphenylacetic acid (164 mg, 0.74 mmol) was dissolved in dichloromethane and cooled to 0° C. Oxalyl chloride (64 μL, 0.74 mmol) was added, then after 5 min, N,N-dimethylformamide (5.7 μL, 0.07 mmol) was added. The reaction stirred at 0° C. for 30 min. and room temperature for 1 h. The solution was added slowly to a mixture of D1 (208 mg, 0.43 mmol) and triethylamine (182 μL, 1.30 mmol) in dichloromethane at −78° C. The mixture was stirred for 30 min., then washed with saturated aqueous sodium bicarbonate and brine. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The resulting product was purified by chromatography (2% methanol with 0.1% ammonium hydroxide in dichloromethane), yielding 265 mg of 4.

Workup

  1. stirringThe mixture was stirred for 30 min.
  2. washwashed with saturated aqueous sodium bicarbonate and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting product was purified by chromatography (2% methanol with 0.1% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-19330e25e2fc45279af397f8b9af4d0b
Source dataset
uspto-grants-2011_05
Patent number
US07939538B2

Reaction notes

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