2-Bromoethanol → HCID 70663349, compound

HRID 878275Notes

Reaction equation

HRID 878275 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:32])[C:15](=[O:31])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([O:26][CH2:27][CH2:28][O:29]C)[CH:17]=2)=[C:4]([O:33][CH3:34])[CH:3]=1.BrCCO.C(=O)([O-])[O-].[K+].[K+].[NH4+].[Cl-]>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:32])[C:15](=[O:31])[C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[C:18]([O:26][CH2:27][CH2:28][OH:29])[CH:17]=2)=[C:4]([O:33][CH3:34])[CH:3]=1

Participants

7

Reactant 4

HCID 108982-Bromoethanol2×HCID 11430Potassium Carbonate2×HCID 25517Ammonium ChlorideHCID 60196594HCID 60196594, compound

Product 1

HCID 70663349HCID 70663349, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-3-hydroxy-N-methyl-5-(trifluoromethyl)benzamide (0.06 g, 143 μmol, Example 236, intermediate) in acetonitrile (2 mL) were added 2-bromoethanol (21.4 mg, 12.1 μL, 171 μmol) and potassium carbonate (23.7 mg, 171 μmol) and the light brown suspension was heated to reflux for 24 hours before another batch of 2-bromoethanol (21.4 mg, 12.1 μL, 171 μmol) and potassium carbonate (29.6 mg, 214 μmol) were added. After heating at reflux for another 20 hours the reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered and evaporated. The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Colorless foam (0.021 g; 31%). MS (ESI): m/z=465.14 [M+H]+.

Workup

  1. temperaturethe light brown suspension was heated
  2. additionwere added
  3. temperatureAfter heating
  4. temperatureat reflux for another 20 hours the reaction mixture
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted twice with EtOAc
  7. dry with materialThe organic layers were dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe product was purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-b1f06d83ea7a41d5a80ea8d3892bf14f
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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