Acetic Acid → HCID 89964983, compound

HRID 1846207Notes

Reaction equation

HRID 1846207 reaction equation
[F:1][C:2]([F:22])([F:21])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2(O)[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[O:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.[Cl:23][CH2:24][C:25]#[N:26].C(O)(=[O:29])C.OS(O)(=O)=O>O.CCOC(C)=O>[Cl:23][CH2:24][C:25]([NH:26][C:10]1([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:22])([F:21])[F:1])=[CH:5][CH:6]=2)[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[O:13][CH2:12][CH2:11]1)=[O:29]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 1118Sulfuric AcidHCID 7856ChloroacetonitrileHCID 89964512HCID 89964512, compound2×

Product 1

HCID 89964983HCID 89964983, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred mixture of 4-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-ol (3 g. 9.6 mmol, Intermediate 3) and 2-chloroacetonitrile (7.2 mL, 128.5 mmol) at 0° C., were added acetic acid (8.68 mL) and conc. H2SO4 (9.45 mL). The ice bath was then removed, and the reaction was stirred at room temperature for 12 h. The progress of reaction was monitored by TLC (50% EtOAc in petroleum ether). The reaction was diluted with H2O (20 mL) and EtOAc (40 mL) and quenched slowly with saturated NaHCO3 (125 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, and concentrated to give the product as a residue. Purification by column chromatography (60-120 mesh silica, 0-50% EtOAc in hexanes) gives the title compound as a white solid. MS (ESI pos. ion) m/z: 387.0 (MH+).

Workup

  1. customThe ice bath was then removed
  2. customThe progress of reaction
  3. customquenched slowly with saturated NaHCO3 (125 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with EtOAc (2×50 mL)
  6. washThe combined organic layers were washed with brine (50 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customto give the product as a residue
  10. customPurification by column chromatography (60-120 mesh silica, 0-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-94c258373ec14791a7c77144a9f1eb53
Source dataset
uspto-grants-2015_02
Patent number
US08952009B2

Reaction notes

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