2-Chloro-4-fluorobenzoyl chloride → HCID 57893667, compound

HRID 1822040Notes

Reaction equation

HRID 1822040 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[N:20]=[C:19]([NH2:21])[CH:18]=[CH:17][CH:16]=2)[CH2:10][C:9]1([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:24][C:25]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:26]=1[C:27](Cl)=[O:28]>O1CCOCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[N:20]=[C:19]([NH:21][C:27](=[O:28])[C:26]3[CH:30]=[CH:31][C:32]([F:34])=[CH:33][C:25]=3[Cl:24])[CH:18]=[CH:17][CH:16]=2)[CH2:10][C:9]1([CH3:23])[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 57893589HCID 57893589, compound

Product 1

HCID 57893667HCID 57893667, compoundYield 11.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Combine 6-(1-benzyl-2,2-dimethyl-piperidin-4-yloxy)-pyridin-2-ylamine (preparation 66, 0.537 g, 1.72 mmol), 1,4-dioxane (20 mL) and 2-chloro-4-fluoro-benzoyl chloride (0.20 g, 1.04 mmol), stir and heat to reflux. After 1.5 hr., cool to ambient temperature and concentrate. Dissolve the residue in methanol (10 mL) and load on an SCX column (10 g); wash with methanol (2×50 mL); elute product with 2M ammonia/methanol (2×50 mL). Concentrate the eluent. Purify the crude mixture by silica gel flash chromatography eluting with 9:1 hexane:ethyl acetate to obtain the title compound (0.056 g 11.5%). Mass spectrum (electrospray): m/z=468.2 (M+1); 1H NMR (CDCl3): 8.3 (bs, 1H), 7.8 (m, 2H), 7.6 (dd, 1H), 7.3 (m, 6H), 7.1 (m, 1H), 6.5 (d, 1H), 5.1 (m, 1H), 3.9 (d, 1H), 3.2 (d, 1H), 2.65 (m, 1H), 2.4 (m, 1H), 2.0 (m, 2H), 1.7 (m, 1H), 1.6 (m, 1H), 1.3 (s, 3H), 1.2 (s, 3H).

Workup

  1. temperatureheat to reflux
  2. concentrationconcentrate
  3. dissolutionDissolve the residue in methanol (10 mL)
  4. washwash with methanol (2×50 mL)
  5. concentrationConcentrate the eluent
  6. customPurify the crude mixture by silica gel flash chromatography
  7. washeluting with 9:1 hexane

Sources & evidence

ORD record
ord-fa6afe0ec64d44e59cd101199237c079
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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