Acetyl chloride → HCID 87738369, compound

HRID 1062308Notes

Reaction equation

HRID 1062308 reaction equation
[F:1][C:2]1[C:3]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=2[CH3:25])=[C:4]([CH:12]=[C:13]([F:16])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].C(N(CC)CC)C.[C:33](Cl)(=[O:35])[CH3:34]>C1COCC1>[F:1][C:2]1[C:3]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=2[CH3:25])=[C:4]([C:5]([NH:7][O:8][CH2:9][CH2:10][O:11][C:33](=[O:35])[CH3:34])=[O:6])[CH:12]=[C:13]([F:16])[C:14]=1[F:15]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 10115851HCID 10115851, compound

Product 1

HCID 87738369HCID 87738369, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2.5 °C

Procedure

To a 0° C. solution of 3,4,5-trifluoro-N-(2-hydroxy-ethoxy)-2-(4-iodo-2-methyl-phenylamino)-benzamide (0.25 g, 0.536 mmol) in THF (10.72 mL) was added triethylamine (0.113 mL, 0.804 mmol). After 5 min, acetyl chloride (0.039 mL, 0.536 mmol) was added to the cold solution, which immediately produced a precipate. After stirring for 50 min between 0-5° C., the reaction mixture was partitioned between water (20 mL) and ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL). The organic layers were combined and dried over anhydrous magnesium sulfate. The resultant mixture was filtered and the filter cake was thoroughly rinsed with ethyl acetate. The filtrate was concentrated in vacuo to obtain a yellow oil (0.1755 g). Chromatographed crude oil using a gradient of hexanes and ethyl acetate. Combined fractions and removed the solvent in vacuo to obtain a solid. The solid was recrystalized in a mixture of hexanes/acetone to afford 0.0221 g (8%) of a solid; 1H NMR (400 MHz, Acetone-d6): δ 10.15 (br s, 1H), 8.49 (br s, 1H), 7.88 (t, J=0.9 Hz, 1H),7.56 (s, 1H), 7.43 (d, J=8.3 Hz, 1H), 6.69 (dd, J=8.55, 5.86 Hz, 1H), 4.53 (br s, 2H), 4.19 (br s, 2H), 2.33 (s, 3H), 1.81 (br s, 3H). 19F NMR (375 MHz, Acetone-d6): δ −139.52 (br t, 1F), −146.62 (br q, 1F), −153.43 (br s, 1F). Anal. Calcd/Found for C18H16F3IN2O4: C, 42.54/40.87; H, 3.17/2.98; N, 5.51/5.17.

Workup

  1. customimmediately produced a precipate
  2. customthe reaction mixture was partitioned between water (20 mL) and ethyl acetate (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe resultant mixture was filtered
  6. washthe filter cake was thoroughly rinsed with ethyl acetate
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-3100205849e04bccb71e795664a6ac01
Source dataset
uspto-grants-2005_11
Patent number
US06960614B2

Reaction notes

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