Tributylphosphine → 3-{4-[1-(4'-Trifluoromethyl-biphenyl-4-yloxymethyl)-heptyl]-benzoylamino}-propionic acid methyl ester

HRID 658311Notes

Reaction equation

HRID 658311 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[CH3:18][O:19][C:20](=[O:41])[CH2:21][CH2:22][NH:23][C:24](=[O:40])[C:25]1[CH:30]=[CH:29][C:28]([CH:31]([CH2:38]O)[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[CH:27][CH:26]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1>[CH3:18][O:19][C:20](=[O:41])[CH2:21][CH2:22][NH:23][C:24](=[O:40])[C:25]1[CH:26]=[CH:27][C:28]([CH:31]([CH2:38][O:15][C:12]2[CH:13]=[CH:14][C:9]([C:6]3[CH:7]=[CH:8][C:3]([C:2]([F:16])([F:17])[F:1])=[CH:4][CH:5]=3)=[CH:10][CH:11]=2)[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 155411804-(4-Trifluoromethylphenyl)phenolHCID 674855693-[4-(1-Hydroxymethyl-heptyl)-benzoylamino]-propionic acid methyl ester

Product 1

HCID 674854863-{4-[1-(4'-Trifluoromethyl-biphenyl-4-yloxymethyl)-heptyl]-benzoylamino}-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 4′-trifluoromethyl-biphenyl-4-ol (213 mg, 0.90 mmol) and 3-[4-(1-hydroxymethyl-heptyl)-benzoylamino]-propionic acid methyl ester (240 mg, 0.72 mmol) in anhydrous toluene (5 mL) is degassed and filled with nitrogen 3 times. Tributylphosphine (270 μL, 1.07 mmol) is added to the reaction mixture under nitrogen at 0° C., followed by addition of 1,1′-(azodicarbonyl)-dipiperidine (271 mg, 1.07 mmol). The reaction mixture is allowed to warm to room temperature and stirred overnight. The mixture is loaded on a silica gel column and purified using hexanes/ethyl acetate. Some racemic ester is hydrolyzed in the next step, and the remaining intermediate ester is sent to chiral chromatography for resolution (see Example 15, Step C). MS (ES): 554.2 [M+H]−.

Workup

  1. additionfilled with nitrogen 3 times
  2. custompurified

Sources & evidence

ORD record
ord-1f779257aa5d4d2996c983d76c7b7156
Source dataset
uspto-grants-2011_12
Patent number
US08076374B2

Reaction notes

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