Thionyl Chloride → HCID 67047920, compound

HRID 606813Notes

Reaction equation

HRID 606813 reaction equation
S(Cl)([Cl:3])=O.[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]2[CH:15]=[N:16][CH:17]=[C:18]([CH:21]=2)[C:19]#[N:20])=[CH:8][C:7]=1[CH2:22]O>C(OCC)(=O)C>[Cl:3][CH2:22][C:7]1[CH:8]=[C:9]([C:12]#[C:13][C:14]2[CH:15]=[N:16][CH:17]=[C:18]([CH:21]=2)[C:19]#[N:20])[CH:10]=[CH:11][C:6]=1[F:5]

Participants

4

Reactant 2

HCID 24386Thionyl Chloride2×HCID 67047751HCID 67047751, compound

Product 1

HCID 67047920HCID 67047920, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Add thionyl chloride (0.59 mL, 8.07 mmol) to a solution of 5-(4-fluoro-3-hydroxymethyl-phenylethynyl)-nicotinonitrile (1.85 g, 7.33 mmol), (prepared as described in EXAMPLE 142). After 3 h add an additional 0.2 mL of thionyl chloride and stir for another 1 h. Dilute the reaction mixture with ethyl acetate and wash with an aqueous saturated solution of sodium bicarbonate and an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate. Purify the crude material by silica gel chromatography, eluting with a gradient from 85:15 to 75:25 hexanes:ethyl acetate, then elute with 50:50 hexanes:ethyl acetate to give the title compound. Further purify by additional silica gel chromatography, eluting with 90:10 (70:30 hexanes:dichloromethane):ethyl acetate. Combine clean fractions from both chromatographies and concentrate to give the title compound as a crystalline solid (1.5 g, 75%).

Workup

  1. washwash with an aqueous saturated solution of sodium bicarbonate
  2. dry with materialDry (sodium sulfate)
  3. filtrationfilter
  4. concentrationconcentrate
  5. customPurify the crude material by silica gel chromatography
  6. washeluting with a gradient from 85:15 to 75:25 hexanes
  7. washethyl acetate, then elute with 50:50 hexanes

Sources & evidence

ORD record
ord-1ff373ec5b184b639c4771deadf8d38c
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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