4-Methylmorpholine → HCID 22612146, compound

HRID 844029Notes

Reaction equation

HRID 844029 reaction equation
[F:1][C:2]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[N:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.CN1CCOCC1.ClC(OCC(C)C)=O.[Cl:34][C:35]1[CH:42]=[CH:41][CH:40]=[CH:39][C:36]=1[CH2:37][NH2:38]>C(Cl)Cl.O>[Cl:34][C:35]1[CH:42]=[CH:41][CH:40]=[CH:39][C:36]=1[CH2:37][NH:38][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][CH:12]=[N:13][C:5]=1[O:4][C:3]1[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:2]=1[F:1]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 666482-ChlorobenzylamineHCID 16790153HCID 16790153, compound

Product 1

HCID 22612146HCID 22612146, compoundYield 66.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(2,4-difluoro-phenoxy)-nicotinic acid (0.300 grams, 1.19 mmole) and NMM (0.133 grams, 1.31 mmole) in dry methylene chloride (15 ml) at −10° C. was added isobutyl chloroformate (0.202 grams, 1.31 mmole). After 20 minutes at −10° C. 2-chlorobenzylamine (0.202 grams, 1.43 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 clear oil that was purified by chromatography on silica gel eluting with 30% ethyl acetate/hexane to give a solid. Recrystalization from ethyl acetate/hexane gave a solid (0.295 g). M.P. 122-124° C.; Anal. calcd. for C19H13N2O2F2Cl: C, 60.89; H, 3.50; N, 7.47. Found: C, 60.77; H, 3.44; N, 7.38.

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 clear oil that
  7. customwas purified by chromatography on silica gel eluting with 30% ethyl acetate/hexane
  8. customto give a solid
  9. customRecrystalization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-492b84d36fc24d89884570956ad4adf4
Source dataset
uspto-grants-2002_04
Patent number
US06380218B1

Reaction notes

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