Phenyl dihydrogen orthoborate → HCID 11166539, compound

HRID 2353362Notes

Reaction equation

HRID 2353362 reaction equation
C([O:5][C:6](=[O:31])[CH2:7][CH2:8][NH:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17]([C:19]3[CH:24]=[CH:23][C:22](Cl)=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)=[CH:16][C:15]=2[CH:30]=1)(C)(C)C.[C:32]1(OB(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[F-].[K+]>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:29][C:26]([F:28])([F:27])[C:21]1[CH:20]=[C:19]([C:17]2[O:18][C:14]3[CH:13]=[CH:12][C:11]([CH2:10][NH:9][CH2:8][CH2:7][C:6]([OH:5])=[O:31])=[CH:30][C:15]=3[CH:16]=2)[CH:24]=[CH:23][C:22]=1[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 78412Phenyl dihydrogen orthoborateHCID 522689Potassium FluorideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 68453850HCID 68453850, compound

Product 1

HCID 11166539HCID 11166539, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-{[2-(4-chloro-3-trifluoromethyl-phenyl)-benzofuran-5-ylmethyl]-amino}-propionic acid tert-butyl ester (1 eq) and phenyl boric acid (1.5 eq) in THF (0.5 M) is added palladium(II) acetate (0.1 eq), 2-(dicyclohexylphosphino)biphenyl (0.2 eq) and potassium fluoride (4.0 eq). The mixture is irradiated with microwave at 120° C. for 45 minutes. The product, 3-{[2-(2-trifluoromethyl-biphenyl-4-yl)-benzofuran-5-ylmethyl]-amino}-propionic acid tert-butyl ester, is purified with column chromatography. The ester is hydrolyzed with TFA in CH2Cl2 (1:2, v/v) at room temperature. It is purified with preparative LCMS to afford 3-{[2-(2-trifluoromethyl-biphenyl-4-yl)-benzofuran-5-ylmethyl]-amino}-propionic acid, which is converted to HCl salt: 1H NMR (400 MHz, CD3OD) δ 8.29 (d, 1H), 8.18 (dd, 1H), 7.82 (d, 1H), 7.71 (d, 1H), 7.55-7.30 (m, 8H), 4.36 (s, 2H), 3.32 (t, 2H), 2.77 (t, 2H); MS (ES) 440.2 (M+H+).

Workup

  1. customThe mixture is irradiated with microwave at 120° C. for 45 minutes
  2. customThe product, 3-{[2-(2-trifluoromethyl-biphenyl-4-yl)-benzofuran-5-ylmethyl]-amino}-propionic acid tert-butyl ester, is purified with column chromatography
  3. customat room temperature
  4. customIt is purified with preparative LCMS

Sources & evidence

ORD record
ord-2e8834dd948f4adf91c2f27ce39520ce
Source dataset
uspto-grants-2010_07
Patent number
US07750021B2

Reaction notes

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