Sodium Hydroxide → 4-Hydroxymethyl ambrisentan

HRID 1513207Notes

Reaction equation

HRID 1513207 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[C:7]([CH3:9])[N:6]=[C:5]([O:10][C@@H:11]([C:16]([O:29][CH3:30])([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:12]([O:14]C)=[O:13])[N:4]=1.[OH-].[Na+]>CO.O>[OH:1][CH2:2][C:3]1[CH:8]=[C:7]([CH3:9])[N:6]=[C:5]([O:10][C@@H:11]([C:16]([O:29][CH3:30])([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:12]([OH:14])=[O:13])[N:4]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 59441450(S)-Methyl 2-(4-(hydroxymethyl)-6-methylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoate

Product 1

HCID 251838154-Hydroxymethyl ambrisentanYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of the compound of Example 11 (0.8 g, 1.96 mmol) in methanol (10 mL) is added a solution of sodium hydroxide (0.392 g, 9.8 mmol) in water (5 mL) and the resultant mixture refluxed for 2 hr. The reaction is cooled to room temperature and the methanol is removed under reduced pressure on a rotary evaporator. The residual aqueous phase is washed with ether (2×10 mL), and then the pH of the aqueous phase is adjusted to 2-3 with 2N sulfuric acid and extracted with ethyl acetate (2×20 mL) to yield the title compound (0.6 g, 80%). MS m/z 395.1 (M+.+1); [α]D20=+141.09° (c=1, CH3OH).

Workup

  1. customthe methanol is removed under reduced pressure on a rotary evaporator
  2. washThe residual aqueous phase is washed with ether (2×10 mL)
  3. extractionextracted with ethyl acetate (2×20 mL)

Sources & evidence

ORD record
ord-df63d1da6df2489795fcf1108c457159
Source dataset
uspto-grants-2012_07
Patent number
US08217155B2

Reaction notes

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