2-Chloro-4-fluorobenzoyl chloride → HCID 57893578, compound

HRID 1822044Notes

Reaction equation

HRID 1822044 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[N:16]=2)[CH2:10][C@@H:9]1[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:23][C:24]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:25]=1[C:26](Cl)=[O:27]>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:26](=[O:27])[C:25]3[CH:29]=[CH:30][C:31]([F:33])=[CH:32][C:24]=3[Cl:23])[N:16]=2)[CH2:10][C@@H:9]1[CH3:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 57893800HCID 57893800, compound

Product 1

HCID 57893578HCID 57893578, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Combine 4-(6-amino-pyridin-2-yloxy)-cis-2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 2 (preparation 64, 0.714 g) and 2-chloro-4-fluorobenzoyl chloride (0.493 g) in 1,4-dioxane (20 mL) and heat. After 2.5 hr., partition between ethyl acetate and saturated aqueous NaCl, dry over anhydrous sodium sulfate, evaporate and purify on a silica gel column eluting with dichloromethane-2M NH3 in methanol, gradient to give the title compound (0.678 g). Mass spectrum (electric spray) m/z=464 (M+1); 1H NMR (CDCl3): 8.45 (br, 1H), 7.89 (br d, 1H), 7.78 (dd, 1H), 7.68 (ddd, 1H), 7.24 (dd, 1H), 7.12 (ddd, 1H), 6.54 (d, 1H), 5.27 (m, 1H), 4.35 (m, 1H), 3.90 (m, 1H), 3.25 (m, 1H), 1.90 (m, 3H), 1.75 (m, 1H), 1.47 (s, 9H), 1.28 (d, 3H).

Workup

  1. temperatureheat
  2. custom, partition between ethyl acetate and saturated aqueous NaCl
  3. dry with materialdry over anhydrous sodium sulfate
  4. customevaporate
  5. custompurify on a silica gel column
  6. washeluting with dichloromethane-2M NH3 in methanol, gradient

Sources & evidence

ORD record
ord-95dd38fa8dfe4e1ead231da69cc575f8
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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