4'-[(4-benzyloxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine methyl ester → 4'-[(4-hydroxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine methyl ester

HRID 29278Notes

Reaction equation

HRID 29278 reaction equation
[CH3:1][O:2][C:3](=[O:44])[C@H:4]([CH:41]([CH3:43])[CH3:42])[NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[O:25][C:26]4[CH:32]=[CH:31][CH:30]=[C:29]([O:33]CC5C=CC=CC=5)[C:27]=4[CH:28]=3)=[O:23])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)(=[O:8])=[O:7]>C(OCC)(=O)C.CO.[Pd]>[CH3:1][O:2][C:3](=[O:44])[C@H:4]([CH:41]([CH3:42])[CH3:43])[NH:5][S:6]([C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:22]([C:24]3[O:25][C:26]4[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[C:27]=4[CH:28]=3)=[O:23])=[CH:19][CH:20]=2)=[CH:13][CH:14]=1)(=[O:7])=[O:8]

Participants

4

Reactant 1

HCID 865990244'-[(4-benzyloxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine methyl ester

Product 1

HCID 687122204'-[(4-hydroxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine methyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 21584119Ethylacetate methanolSolvent

Procedure

The product of Example 13-Step 1, 4′-[(4-benzyloxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine methyl ester (0.32 mmol), was dissolved in 3 mL of ethyl acetate-MeOH (2:1) and 10% Pd/C (20 mg) was added. The reaction was stirred under a hydrogen atmosphere for 5 h. The reaction mixture was filtered through celite and then concentrated to give 4′-[(4-hydroxy-benzofuran-2-carbonyl)-amino]-biphenyl-4-sulfonyl-L-valine methyl ester in 80% yield. The product (0.13 mmol) was dissolved in anhydrous DMF (1 mL), and Cs2CO3 (0.26 mmol) was added, followed by 2-bromo-propionic acid ethyl ester (0.13 mmol). After the reaction was complete by TLC the reaction was diluted with ethyl acetate and acidified with 1N hydrochloric acid. The organic layer was washed with brine (2×), dried (magnesium sulfate), filtered and concentrated to afford 79 mg of 4′-{[4-(1-ethoxycarbonyl-ethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonyl-L-valine methyl ester. The ester was taken up in THF:MeOH (2:1, 2 mL) and treated with NaOH (5N, 5 eq). The reaction was stirred overnight, diluted with ethyl acetate and acidified with 1N HCl. The organic layer was isolated and washed with brine (2×), dried (magnesium sulfate), filtered and concentrated to afford 4′-{[4-(1-carboxy-ethoxy)-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonyl-L-valine. LCMS MH+ (m/z) 581. 1H NMR (300 MHz, CD3OD): δ 7.91-7.68 ppm (m, 6H), 7.40-7.09 ppm (m, 3H), 6.70 ppm (d, 1H, J=8 Hz), 4.99 ppm (q, 1H, J=13 Hz), 3.69 ppm (d, 1H, J=5.8 Hz), 2.08-2.00 ppm (m, 1H), 1.69 ppm (d, 3H, J=6.9 Hz), 0.97 ppm (d, 3H, J=7.0 Hz), 0.96 ppm (d, 3H, J=7.0 Hz).

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-1edd8fe979544e66916d997c64ff8f1f
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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