Diisopropylamine → ethyl (alphaS)-alpha-[[(1,1-dimethylethoxy)carbonyl]amino]-4'-ethoxymethyl-2',6'-dimethoxy(1,1'-biphenyl)-4-propionate

HRID 1454108Notes

Reaction equation

HRID 1454108 reaction equation
[CH3:1][C:2]([CH3:29])([O:4][C:5]([NH:7][C@@H:8]([CH2:14][C:15]1[CH:20]=[CH:19][C:18](OS(C(F)(F)F)(=O)=O)=[CH:17][CH:16]=1)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:6])[CH3:3].[CH2:30]([O:32][CH2:33][C:34]1[CH:39]=[C:38]([O:40][CH3:41])[C:37](OB(O)O)=[C:36]([O:46][CH3:47])[CH:35]=1)[CH3:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NC(C)C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1.CN1CCCC1=O>[CH3:1][C:2]([CH3:29])([O:4][C:5]([NH:7][C@@H:8]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:37]2[C:36]([O:46][CH3:47])=[CH:35][C:34]([CH2:33][O:32][CH2:30][CH3:31])=[CH:39][C:38]=2[O:40][CH3:41])=[CH:17][CH:16]=1)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:6])[CH3:3]

Participants

9

Reactant 4

HCID 7912DiisopropylamineHCID 11776TriphenylphosphineHCID 10789275(S)-Ethyl 2-((tert-butoxycarbonyl)amino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propanoateHCID 230809502,6-Dimethoxy-4-(ethoxymethyl)phenylboric acid

Product 1

HCID 11329259ethyl (alphaS)-alpha-[[(1,1-dimethylethoxy)carbonyl]amino]-4'-ethoxymethyl-2',6'-dimethoxy(1,1'-biphenyl)-4-propionateYield 123.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

Under nitrogen atmosphere, to a mixture of ethyl (αS)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-4-(trifluoromethanesulfonyloxy)benzenepropionate (66.2 g), 4-ethoxymethyl-2,6-dimethoxyphenylboric acid (54.0 g), triphenylphosphine (9.83 g) and N-methylpyrrolidone (330 ml) were added palladium acetate (1.68 g) and diisopropylamine (24.9 g), and the mixture was heated at 90° C. After stirring for 1 hour at the same temperature, the mixture was cooled and toluene and water were added. The organic layers were washed with 10% aqueous citric acid solution and saturated aqueous NaCl solution and dried over magnesium sulfate. The solvent was removed in vacuo to yield ethyl (αS)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-4′-ethoxymethyl-2′,6′-dimethoxy(1,1′-biphenyl)-4-propionate (90.1 g) as oil.

Workup

  1. temperaturethe mixture was cooled
  2. washThe organic layers were washed with 10% aqueous citric acid solution and saturated aqueous NaCl solution
  3. dry with materialdried over magnesium sulfate
  4. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-b1731374eedf48cfbe30d4cba0c11c28
Source dataset
uspto-grants-2009_01
Patent number
US07476758B2

Reaction notes

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