4-Methylmorpholine → HCID 67153380, compound

HRID 1160936Notes

Reaction equation

HRID 1160936 reaction equation
[Br:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][CH:7]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=2)[CH2:8][CH2:9][CH2:10][C:11]([F:14])([F:13])[F:12])=[CH:4][CH:3]=1.ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.Cl.[CH3:45][O:46][C:47](=[O:51])[CH2:48][CH2:49][NH2:50]>ClCCl.O>[CH3:45][O:46][C:47](=[O:51])[CH2:48][CH2:49][NH:50][C:19](=[O:21])[C:18]1[CH:22]=[CH:23][C:15]([CH:7]([O:6][C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:25][CH:24]=2)[CH2:8][CH2:9][CH2:10][C:11]([F:12])([F:13])[F:14])=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 67153485HCID 67153485, compound

Product 1

HCID 67153380HCID 67153380, compoundYield 78.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Racemic 4-[1-(4-bromo-phenoxy)-5,5,5-trifluoro-pentyl]-benzoic acid (7.46 g, 17.89 mmol), 2-chloro-4,6-dimethoxy-1,3,5-triazine (3.23 g, 18.43 mmol) and 4-methylmorpholine (2.07 mL, 18.78 mmol) are combined in anhydrous dichloromethane (100 mL) under nitrogen. The reaction is allowed to stir under nitrogen at room temperature overnight. Beta alanine methyl ester hydrochloride (2.76 g, 19.68 mmol) and 4-methylmorpholine (4.14 mL, 37.56 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 (7.07 g, 14.1 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-70c99922bf7d43fbbeef8257c1d82825
Source dataset
uspto-grants-2010_10
Patent number
US07816557B2

Reaction notes

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