Water → 2-(4-{[(3-Tert-butoxycarbonylmethoxy-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenyl)-2-methyl-propionic acid ethyl ester

HRID 23793

Reaction equation

HRID 23793 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:28])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][NH:18][S:19]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)(=[O:21])=[O:20])[CH:12]=1)([CH3:6])([CH3:5])[CH3:4].[CH2:29]([O:31][C:32](=[O:44])[C:33]([C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Br)=[CH:38][CH:37]=1)([CH3:35])[CH3:34])[CH3:30].O>CN(C=O)C>[CH2:29]([O:31][C:32](=[O:44])[C:33]([C:36]1[CH:41]=[CH:40][C:39]([CH2:42][N:18]([CH2:17][C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([O:10][CH2:9][C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:28])[CH:12]=2)[S:19]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)(=[O:21])=[O:20])=[CH:38][CH:37]=1)([CH3:34])[CH3:35])[CH3:30]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 154287362-(4-Bromomethyl-phenyl)-2-methyl-propionic acid ethyl esterHCID 69730626{3-[(Pyridine-3-sulfonylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester

Product 1

HCID 697317692-(4-{[(3-Tert-butoxycarbonylmethoxy-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenyl)-2-methyl-propionic acid ethyl esterYield 48.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent4×

Conditions

Temperature
0 °C

Procedure

NaH (60% by weight in oil, 23 mg, 0.55 mmol) was washed with DMF (5 mL) and fresh DMF (5 mL) was added. The reaction was cooled to 0° C. and a solution of {3-[(pyridine-3-sulfonylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester (184 mg, 0.486 mmol) in DMF (1 mL) was added. The reaction was stirred for 1 h and 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid ethyl ester (145 mg, 0.51 mmol) in DMF (1 mL) was added. The reaction was warmed to room temperature and was heated at 100° C. for 2 h. Water was added and the aqueous solution was washed with EtOAc (3×). The combined organic solutions were washed with water (5×), dried (MgSO4), filtered and concentrated. Flash chromatography (2:1 hexanes:EtOAc) provided 2-(4-{[(3-tert-butoxycarbonylmethoxy-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenyl)-2-methyl-propionic acid ethyl ester (138 mg). 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.76 (m, 1H), 7.97 (m, 1H), 7.40 (m, 1H), 7.19 (d, 2H), 7.13 (m, 1H), 7.02 (d, 2H), 6.76 (m, 1H), 6.67 (m, 2H), 4.41 (s, 2H), 4.33 (s, 4H), 4.10 (q, 2H), 1.52 (s, 6H), 1.49 (s, 9H), 1.17 (t, 3H).

Workup

  1. additionwas added
  2. temperatureThe reaction was warmed to room temperature
  3. temperaturewas heated at 100° C. for 2 h
  4. washthe aqueous solution was washed with EtOAc (3×)
  5. washThe combined organic solutions were washed with water (5×)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e1755960f5b44f6dbd8fbde213a857ba
Source dataset
uspto-grants-2005_02
Patent number
US06852863B2

Linked notes

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