Acetic Anhydride → HCID 86602506, compound

HRID 1822135Notes

Reaction equation

HRID 1822135 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:17])([C:13]([F:16])([F:15])[F:14])[C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[Cl:18].[CH3:19][C:20](OC(C)=O)=[O:21]>N1C=CC=CC=1>[Cl:18][C:3]1[CH:4]=[C:5]([C:8]([OH:17])([C:9]([F:10])([F:11])[F:12])[C:13]([F:14])([F:15])[F:16])[CH:6]=[CH:7][C:2]=1[NH:1][C:20](=[O:21])[CH3:19]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 14510516HCID 14510516, compound

Product 1

HCID 86602506HCID 86602506, compoundYield 96.4%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 1 g (3.4 mmol) of 2-(4-amino-3-chloro-phenyl)-1,1,1,3,3,3-hexafluoro-propan-2-ol in 5 mL of pyridine was treated with 0.42 mL (4.4 mmol) of Ac2O and stirred at 70° C. for 10 hours. The solvent was evaporated, the residue dissolved in THF, treated with a 2M aqueous solution of NaOH and stirred for 1 h at RT. After acidification of the mixture to a pH of ca. 7 by adding aqueous HCl, Et2O and H2O were added, the phases were separated and the aqueous one was extracted with Et2O. The combined organic phases were dried over Na2SO4 and evaporated to yield 1.1 g (ca. 94%) of crude N-[2-chloro-4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-acetamide, which was dissolved in 20 mL of DMF and treated with 0.65 mL (4.37 mmol) of DBU and then at 0° C. dropwise with 0.73 mL (4.37 mmol) of TESCl. The mixture was stirred overnight and poured into a mixture of a saturated aqueous solution of NH4Cl and Et2O. The phases were separated and the aqueous one extracted with Et2O. The combined organic phases were dried over Na2SO4 and evaporated to yield 1.53 g (93%) of crude N-[2-chloro-4-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-phenyl]-acetamide, yellow oil, MS: 450 (MH+, 1Cl).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in THF
  3. additiontreated with a 2M aqueous solution of NaOH
  4. stirringstirred for 1 h at RT
  5. additionAfter acidification of the mixture to a pH of ca. 7 by adding aqueous HCl, Et2O and H2O
  6. additionwere added
  7. customthe phases were separated
  8. extractionthe aqueous one was extracted with Et2O
  9. dry with materialThe combined organic phases were dried over Na2SO4
  10. customevaporated

Sources & evidence

ORD record
ord-da7d4df3dfe04e13820d774f940a43a7
Source dataset
uspto-grants-2009_10
Patent number
US07608721B2

Reaction notes

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