4-Methylmorpholine → HCID 178501296, compound

HRID 2269534Notes

Reaction equation

HRID 2269534 reaction equation
CN1CCOCC1.[N+:8]([C:11]1[N:12]=[C:13]([CH:16]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([OH:19])=O)[NH:14][CH:15]=1)([O-:10])=[O:9].ClC1N=C(OC)N=C(OC)N=1.Cl.[CH3:38][O:39][C:40](=[O:46])[C@@H:41]1[CH2:45][CH2:44][CH2:43][NH:42]1>O1CCCC1.C(OC)(C)(C)C.CO.C(Cl)Cl>[N+:8]([C:11]1[N:12]=[C:13]([CH:16]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([N:42]2[CH2:43][CH2:44][CH2:45][C@H:41]2[C:40]([O:39][CH3:38])=[O:46])=[O:19])[NH:14][CH:15]=1)([O-:10])=[O:9]

Participants

9

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 2733200methyl L-prolinate hydrochlorideHCID 178525051HCID 178525051, compound

Product 1

HCID 178501296HCID 178501296, compoundYield 60.2%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

N-Methyl morpholine (17.79 ml, 2 eq) was added to a stirred solution of 2-(4-nitroimidazolyl)-2-phenylacetic acid (1) (20 g, 80.9 mm) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (14.45 g,80.1 mm, 1.0 eq) in 175 ml of anhydrous tetrahydrofuran at 25° C. After stirring the reaction mixture at ambient temperature for 1.5 h, 14.45g (80.9 mm, 1.0 eq) of proline methyl ester hydrochloride was added. The reaction was stirred overnight at room temperature and the solvent was evaporated under a stream of nitrogen. The residue was partitioned between 200 Ml of 1M HCl and 200 mL of deionized water. The layers were separated and the organic layer was washed with saturated sodium bicarbonate solution. A quantity of water sufficient to dissolve the resulting solids was added. The organic layer was washed with brine, dried over magnesium sulfate, filtered and the volatiles were removed under vacuum to give a brown foam. The foam was dissolved in methyl t-butyl ether, methylene chloride and methanol to effect crystallization. The resulting slurry was filtered and dried under vacuum to give 17.45 g (60%) of a cream colored product MS: 358 (M+) IR (cm−1): 1744, 1668; H1 nmr d (d6 DMSO): 1.42-1.46 (m, 3H), 1.6-1.9 (m, 1H), 2.42-2.63 (m,1H), 3.21 (s, 1.5H), 3.25 (s, 1.5H), 3.30-3.36 (m, 1H), 4.01-4.06 (m, 1H), 6.36 (s, 0.5H), 6.43 (s, 0.5h), 7.0-7.2 (m, 5H), 7.38 (s, 0.5H), 7.41 (s, 0.5H), 7.75 (s, 0.5H), 7.83 (s, 0.5H)

Workup

  1. stirringThe reaction was stirred overnight at room temperature
  2. customthe solvent was evaporated under a stream of nitrogen
  3. customThe residue was partitioned between 200 Ml of 1M HCl and 200 mL of deionized water
  4. customThe layers were separated
  5. washthe organic layer was washed with saturated sodium bicarbonate solution
  6. dissolutionA quantity of water sufficient to dissolve the resulting solids
  7. additionwas added
  8. washThe organic layer was washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customthe volatiles were removed under vacuum
  12. customto give a brown foam
  13. customcrystallization
  14. filtrationThe resulting slurry was filtered
  15. customdried under vacuum

Sources & evidence

ORD record
ord-0b1de089a245466aa1d80cc20360200b
Source dataset
uspto-grants-2001_12
Patent number
US06329342B1

Reaction notes

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