Sodium Hydroxide → HCID 58488448, compound

HRID 2194912Notes

Reaction equation

HRID 2194912 reaction equation
[NH2:1][CH2:2][CH:3]([C:24]1[CH:25]=[C:26]([C:41]([O:43]C)=[O:42])[C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH2:36][CH2:37][CH2:38][O:39][CH3:40])=[CH:28][CH:29]=1)[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][O:14][C:15]2[C:20]([Cl:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=2[Cl:23])=[CH:7][CH:6]=1.[OH-].[Na+]>CCOCC.CCOC(C)=O>[NH2:1][CH2:2][CH:3]([C:24]1[CH:25]=[C:26]([C:41]([OH:43])=[O:42])[C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH2:36][CH2:37][CH2:38][O:39][CH3:40])=[CH:28][CH:29]=1)[CH2:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][CH2:13][O:14][C:15]2[C:20]([Cl:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=2[Cl:23])=[CH:9][CH:10]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67445693HCID 67445693, compound

Product 1

HCID 58488448HCID 58488448, compound

Reagents, catalysts & solvents 1

HCID 21584169Diethylether ethylacetateSolvent

Procedure

To a solution of methyl 4-(2-amino-1-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-benzyl}ethyl)-2′-(3-methoxypropyl)biphenyl-2-carboxylate (1.0 eq.; EXAMPLE 22) in THF/MeOH (1/1; 0.09M) was added aqueous sodium hydroxide (1N; 3 eq.). The mixture was stirred in a microwave (Smith Creator; Personal Chemistry),) at 120° C. for 80 min. The resulting mixture was cooled to room temperature quenched with excess acetic acid and concentrated. The residue was diluted with EtOAc, washed with water, brine, dried over Na2SO4, filtered and concentrated. Purification by column chromatography on silica gel, eluting with CH2Cl2/MeOH(NH3; 2M) 5% afforded the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ 7.50 (br s, 0.5H), 7.44 (br s, 0.5H), 7.25-7.11 (m, 6H), 7.11-7.03 (m, 4H), 6.87-6.81 (m, 2H), 4.36-4.27 (m, 4H), 3.30-3.21 (m, 8H), 3.01-2.91 (m, 2H), 2.65-2.53 (m, 2H), 2.30 (s, 3H), 1.77-1.64 (m, 2H) (mixture of rotamers). LRMS ESI [M+H]; 622.2

Workup

  1. customquenched with excess acetic acid
  2. concentrationconcentrated
  3. additionThe residue was diluted with EtOAc
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography on silica gel
  9. washeluting with CH2Cl2/MeOH(NH3; 2M) 5%

Sources & evidence

ORD record
ord-2e3d8906cc0442fb8ebf0bc7d8f088bf
Source dataset
uspto-grants-2012_12
Patent number
US08334308B2

Reaction notes

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