4-Methylmorpholine → cis-3-(4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoylamino)-propionic acid methyl ester

HRID 1669309Notes

Reaction equation

HRID 1669309 reaction equation
[F:1][C:2]([F:34])([F:33])[CH2:3][CH2:4][CH:5]([C:17]1[CH:18]=[N:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=2)=[CH:21][CH:22]=1)/[CH:6]=[CH:7]\[C:8]1[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][CH:9]=1.Cl[C:36]1[C:37]([O:44][CH3:45])=NN=[N:40][C:41]=1OC.CN1CC[O:50]CC1.Cl.NCCC(O)=O>C(Cl)Cl.O>[CH3:45][O:44][C:37](=[O:50])[CH2:36][CH2:41][NH:40][C:12](=[O:13])[C:11]1[CH:15]=[CH:16][C:8](/[CH:7]=[CH:6]\[CH:5]([C:17]2[CH:18]=[N:19][C:20]([C:23]3[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:28]=3)=[CH:21][CH:22]=2)[CH2:4][CH2:3][C:2]([F:1])([F:33])[F:34])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 12201475beta-Alanine HydrochlorideHCID 12493616Chloro-dimethoxy-triazineHCID 86620359Cis-4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid

Product 1

HCID 86620361cis-3-(4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoylamino)-propionic acid methyl esterYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

The cis-4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid (214 mg, 0.45 mmol), chloro-dimethoxy-triazine (CDMT) (81 mg, 0.46 mmol), and 4-methylmorpholine (50 uL, 0.47 mmol) are combined in anhydrous DCM under nitrogen. The reaction is allowed to stir under nitrogen at room temperature overnight. Beta-alanine hydrochloride (68 mg, 0.49 mmol) and 4-methylmorpholine (100 uL, 0.94 mmol) is then 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 DCM and water and rinsed with 1N HCl. The organic layer is washed with water and brine, dried over anhydrous sodium sulfate, then filtered and concentrated. The cis-3-(4-{6,6,6-trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoylamino)-propionic acid methyl ester (197 mg, 0.35 mmol) is isolated after column chromatography, 78% yield.

Workup

  1. stirringto stir at room temperature
  2. customupon complete consumption of the acid
  3. additionthe reaction is diluted with DCM and water
  4. washrinsed with 1N HCl
  5. washThe organic layer is washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0c95d264155e4ba3b071f18826fcb363
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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