4-Methylmorpholine → HCID 24764225, compound

HRID 1009838Notes

Reaction equation

HRID 1009838 reaction equation
[N:1]1([C:5]([C:7]2[CH:31]=[CH:30][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([O:21][C@@H:22]([CH3:29])[CH2:23][O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH:20]=3)[C:15]([OH:17])=O)=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.Cl[C:33]1[N:38]=C(OC)N=C(OC)[N:34]=1.C[N:44]1[CH2:49][CH2:48]OC[CH2:45]1.CNN1C=CC=N1>O.C(#N)C>[N:1]1([C:5]([C:7]2[CH:8]=[CH:9][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([O:21][C@@H:22]([CH3:29])[CH2:23][O:24][C:25]([CH3:26])([CH3:27])[CH3:28])[CH:20]=3)[C:15]([NH:38][C:33]3[CH:48]=[CH:49][N:44]([CH3:45])[N:34]=3)=[O:17])=[CH:30][CH:31]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 14572871HCID 14572871, compoundHCID 16740072HCID 16740072, compound

Product 1

HCID 24764225HCID 24764225, compoundYield 92.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

3-[4-(Azetidin-1-ylcarbonyl)phenoxy]-5-[(1S)-2-tert-butoxy-1-methylethoxy]benzoic acid (6.18 mmol, 2.64 g) and acetonitrile (18.5 mL) were charged to a vessel. The contents were stirred and cooled to 0° C. 2-Chloro-4,6-dimethoxy-1,3,5-triazine (6.78 mmol, 1.19 g) was added to the slurry followed by an addition of N-methylmorpholine (8.11 mmol, 0.82 g), added over 20 minutes. The reaction was held for approximately 1 hour at 0° C. and allowed to warm up to ambient. N-methylaminopyrazole (6.79 mmol, 0.66 g) was added over 20 minutes and the reaction held at ambient temperature until the reaction was complete. Water (7 mL) was added to the reaction mixture and the acetonitrile removed by distillation at reduced pressure. Ethyl acetate (32 mL), water (7 mL) and sodium bicarbonate solution (10% by weight, 26 mL) were added to the resultant slurry. The bi-phasic liquor was separated and the ethyl acetate phase sequentially washed with further sodium bicarbonate (10% by weight, 13 mL), water (13 mL), 2M hydrochloric acid (2×13 mL), and then with water (2×13 mL). The washed organic phase was azeodistilled at reduced pressure, removing water and solvent, to give a light brown foam (2.9 g, 90% yield).

Workup

  1. additionadded over 20 minutes
  2. temperatureto warm up to ambient
  3. customheld at ambient temperature until the reaction
  4. customthe acetonitrile removed by distillation at reduced pressure
  5. additionEthyl acetate (32 mL), water (7 mL) and sodium bicarbonate solution (10% by weight, 26 mL) were added to the resultant slurry
  6. customThe bi-phasic liquor was separated
  7. washthe ethyl acetate phase sequentially washed with further sodium bicarbonate (10% by weight, 13 mL), water (13 mL), 2M hydrochloric acid (2×13 mL)
  8. customremoving water and solvent

Sources & evidence

ORD record
ord-d67a5c59a44942feb63149fcd48de2a7
Source dataset
uspto-grants-2011_07
Patent number
US07973178B2

Reaction notes

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