4-Methylmorpholine → (+/-)-3-{4-[2-Cyclohexyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-ethoxy]-3-methyl-benzoylamino}-2-methyl-propionic acid ethyl ester

HRID 1669277Notes

Reaction equation

HRID 1669277 reaction equation
[CH:1]1([CH2:7][CH:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[O:9][C:10]2[CH:18]=[CH:17][C:13](C(O)=O)=[CH:12][CH:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:36]1[N:41]=[C:40]([O:42]C)N=C(OC)N=1.[CH3:46]N1CCOCC1.[CH2:53]([O:55][C:56](=[O:61])[CH:57](O)[CH2:58]N)[CH3:54]>C1COCC1.CCOC(C)=O.O>[CH2:53]([O:55][C:56](=[O:61])[CH:57]([CH3:58])[CH2:36][NH:41][C:40](=[O:42])[C:13]1[CH:12]=[CH:11][C:10]([O:9][CH:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:7][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)=[C:18]([CH3:46])[CH:17]=1)[CH3:54]

Participants

8

Reactant 4

HCID 79724-Methylmorpholine2×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 21834752Ethyl 3-amino-2-hydroxypropanoateHCID 59729441(+/-)-4-[2-Cyclohexyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-ethoxy]-benzoic acid

Product 1

HCID 67341724(+/-)-3-{4-[2-Cyclohexyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-ethoxy]-3-methyl-benzoylamino}-2-methyl-propionic acid ethyl esterYield 56%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (±)-4-[2-cyclohexyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethoxy]-benzoic acid (0.0813 g, 0.174 mmol) in THF (1.7 mL) is treated with 2-chloro-4,6-dimethoxy-[1,3,5]triazine (CDMT, 0.0338 g, 0.193 mmol) and N-methyl morpholine (NMM, 0.020 mL, 0.27 mmol). The mixture is added to a flask containing (±)-3-amino-2-hydroxy-propionic acid ethyl ester (0.0465 g, 0.274 mmol). Additional NMM (0.030 mL, 0.273 mmol) and H2O (0.4 mL) are added and the reaction is stirred overnight. The reaction mixture is dissolved in EtOAc (10 mL) and washed with 0.1 N HCl (2×10 mL), ph=7 phosphate buffer (1×), brine (1×), dried over MgSO4, filtered, and conc. The residue is loaded onto silica gel and eluted with hexanes using a gradient of 10% EtOAc to 60% EtOAc giving (±)-3-{4-[2-cyclohexyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethoxy]-3-methyl-benzoylamino}-2-methyl-propionic acid ethyl ester (0.0568 g, 56%) as a white foam. MS (ES): 582.3 [M−H]−.

Workup

  1. additionThe mixture is added to a flask
  2. washwashed with 0.1 N HCl (2×10 mL), ph=7 phosphate buffer (1×), brine (1×)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. washeluted with hexanes using a gradient of 10% EtOAc to 60% EtOAc

Sources & evidence

ORD record
ord-6db01be673ce4679b78a68fb5dfa4e1f
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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