4-Methylmorpholine → HCID 67153416, compound

HRID 1914346Notes

Reaction equation

HRID 1914346 reaction equation
[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([S:9][CH:10]([C:18]2[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=2)[CH2:11][CH2:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[CH:4][C:3]=1[CH3:27].ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.Cl.[CH2:47]([O:49][C:50](=[O:54])[CH2:51][CH2:52][NH2:53])[CH3:48]>ClCCl.O>[CH2:47]([O:49][C:50](=[O:54])[CH2:51][CH2:52][NH:53][C:22](=[O:23])[C:21]1[CH:25]=[CH:26][C:18]([CH:10]([S:9][C:5]2[CH:6]=[C:7]([CH3:8])[C:2]([Br:1])=[C:3]([CH3:27])[CH:4]=2)[CH2:11][CH2:12][CH2:13][C:14]([F:17])([F:15])[F:16])=[CH:19][CH:20]=1)[CH3:48]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 67153422HCID 67153422, compound

Product 1

HCID 67153416HCID 67153416, compoundYield 87.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Racemic 4-[1-(4-bromo-3,5-dimethyl-phenylsulfanyl)-5,5,5-trifluoro-pentyl]-benzoic acid (0.190 g, 0.410 mmol), 2-chloro-4,6-dimethoxy-1,3,5-triazine (0.0747 g, 0.430 mmol) and 4-methylmorpholine (0.050 mL, 0.430 mmol) are combined in anhydrous dichloromethane (2.0 mL) under nitrogen. The reaction is allowed to stir under nitrogen at room temperature overnight. The beta alanine ethyl ester hydrochloride (0.0695 g, 0.450 mmol) and 4-methylmorpholine (0.100 mL, 0.860 mmol) is added to the reaction mixture and allowed to stir at room temperature. Some water (<10% volume) is added to help solubility. The reaction is monitored by HPLC, and upon complete consumption of the acid, the reaction is diluted with dichloromethane. The reaction is diluted with water and rinsed with 1N hydrochloric acid. Upon acidification, the two layers are separated. The organic layer is washed with brine, dried over anhydrous sodium sulfate, and concentrated. Flash column chromatography gave the title compound (0.200 g, 0.360 mmol).

Workup

  1. stirringto stir at room temperature
  2. customupon complete consumption of the acid
  3. additionthe reaction is diluted with dichloromethane
  4. additionThe reaction is diluted with water
  5. washrinsed with 1N hydrochloric acid
  6. customUpon acidification, the two layers are separated
  7. washThe organic layer is washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3a5263ac63c54179a825fe7f2daf0866
Source dataset
uspto-grants-2013_12
Patent number
US08609892B2

Reaction notes

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