Water → HCID 10907217, compound

HRID 398195Notes

Reaction equation

HRID 398195 reaction equation
[CH3:1][O:2][C:3](=[O:38])[C:4]([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH:17]([NH:23][C:24]([C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:28][CH:27]=2)=[O:25])[C:18](=O)[CH2:19][CH2:20][CH3:21])=[CH:10][CH:9]=1)([CH3:6])[CH3:5].P(Cl)(Cl)(Cl)=O.O.[OH-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:38])[C:4]([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:23]=[C:24]([C:26]3[CH:31]=[CH:30][C:29]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[CH:28][CH:27]=3)[O:25][C:18]=2[CH2:19][CH2:20][CH3:21])=[CH:10][CH:9]=1)([CH3:6])[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 11827416HCID 11827416, compound

Product 1

HCID 10907217HCID 10907217, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A sample of 2-(4-{3-[(biphenyl-4-carbonyl)-amino]-4-oxo-heptyloxy}-phenoxy)-2-methyl-propionic acid methyl ester (514 mg, 0.99 mmol) was dissolved in 6 mL of dry DMF followed by addition of phosphorus oxychloride (0.28 mL, 2.88 mmol, 3 equiv.). The mixture was heated at 90° C. for 20 minutes under a nitrogen atmosphere. The reaction mixture was then allowed to cool to room temperature followed by addition of cold water (10 mL) and additional stirring for 10 minutes. Sufficient 1.0 N NaOH was then added to achieve neutral pH. The mixture was partitioned between ethyl ether (100 mL) and water (50 mL). The aqueous layer was back-extracted with ethyl ether (100 mL) and the organic phases combined, which were then washed with 5% aq LiCl, dried over NaCl, and concentrated in vacuo to yield an oil which was immediately subjected to silica gel chromatography (ethyl acetate/hexanes) to yield 484 mg (98%) of an oil. HPLC RT1=12.70 min; 1H NMR (400 MHz, CDCl3) δ8.02 (d, J=8.3 Hz, 2H), 7.64-7.58 (m, 4H), 7.43-7.33 (m, 3H), 6.78-6.72 (m, 4H), 4.17 (t, J=6.3 Hz, 2H), 3.73 (s, 3H), 2.94 (t, J=6.3 Hz, 2H), 2.66 (t, J=7.3 Hz, 2H), 1.73-1.67 (m, 2H), 1.48 (s, 6H), 0.97 (t, J=7.3 Hz, 3H); MS (EI) 500.1 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. customThe mixture was partitioned between ethyl ether (100 mL) and water (50 mL)
  3. extractionThe aqueous layer was back-extracted with ethyl ether (100 mL)
  4. washwhich were then washed with 5% aq LiCl
  5. dry with materialdried over NaCl
  6. concentrationconcentrated in vacuo
  7. customto yield an oil which

Sources & evidence

ORD record
ord-6f01133e91984f5a8d694dd0512ef216
Source dataset
uspto-grants-2003_08
Patent number
US06610696B2

Reaction notes

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