4-Methylmorpholine → N-(2-Chloro-benzyl)-2-(3-fluoro-phenoxy)-nicotinamide

HRID 844030Notes

Reaction equation

HRID 844030 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[O:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=O.CN1CCOCC1.ClC(OCC(C)C)=O.[Cl:33][C:34]1[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36][NH2:37]>C(Cl)Cl.O>[Cl:33][C:34]1[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36][NH:37][C:8](=[O:10])[C:7]1[CH:11]=[CH:12][CH:13]=[N:14][C:6]=1[O:5][C:4]1[CH:15]=[CH:16][CH:17]=[C:2]([F:1])[CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 666482-ChlorobenzylamineHCID 122026432-(3-Fluorophenoxy)nicotinic acid

Product 1

HCID 22612076N-(2-Chloro-benzyl)-2-(3-fluoro-phenoxy)-nicotinamideYield 71.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(3-Fluoro-phenoxy)-nicotinic acid (0.300 grams, 1.29 mmole) and NMM (0.144 grams, 1.41 mmole) in dry methylene chloride (15 ml) at −10° C. was added isobutyl chloroformate (0.193 grams, 1.41 mmole). After 20 minutes at −10° C. 2-chlorobenzylamine (0.219 grams, 1.55 mmole) was added and the mixture was allowed to warm to room temperature over night. The mixture was poured into water and extracted with ethyl acetate. The combined organics were washed with 1 N NaOH, water and brine, dried over MgSO4, filtered and concentrated to give a solid that was purified by chromatography on silica gel eluting with 30% ethyl acetate/hexane to give a white solid. Recrystalization from ethyl acetate/hexane gave a solid (0.328 g). M.P. 115-117° C.; Anal. calcd. for C19H14N2O2ClF: C, 63.96; H, 3.95; N, 7.85. Found: C, 64.04; H, 3.92; N, 7.85.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organics were washed with 1 N NaOH, water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a solid
  7. customthat was purified by chromatography on silica gel eluting with 30% ethyl acetate/hexane
  8. customto give a white solid
  9. customRecrystalization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-5f3cf834b84044e79d0f98a655bec5e8
Source dataset
uspto-grants-2002_04
Patent number
US06380218B1

Reaction notes

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