Methanol → 2-(3-ethoxy-4-propan-2-yloxyphenyl)-2-[4-(N-phenylmethoxycarbonylcarbamimidoyl)anilino]acetic acid

HRID 1438186Notes

Reaction equation

HRID 1438186 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([NH:20][CH:21]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH:33]([CH3:35])[CH3:34])=[C:28]([O:36][CH2:37][CH3:38])[CH:27]=2)[C:22]([O:24]C)=[O:23])=[CH:16][CH:15]=1)=[NH:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+].CO>C1COCC1>[CH2:1]([O:8][C:9]([NH:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([NH:20][CH:21]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH:33]([CH3:34])[CH3:35])=[C:28]([O:36][CH2:37][CH3:38])[CH:27]=2)[C:22]([OH:24])=[O:23])=[CH:16][CH:15]=1)=[NH:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 148550093HCID 148550093, compound

Product 1

HCID 1527550322-(3-ethoxy-4-propan-2-yloxyphenyl)-2-[4-(N-phenylmethoxycarbonylcarbamimidoyl)anilino]acetic acidYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 141E (4.64 g, 8.9 mmol) in THF (20 mL) was added lithium hydroxide (17.8 mL, 1M, 17.8 mmol) then methanol (5 mL). After stirring for 2 h at rt, the reaction was concentrated and redissolved in ethyl acetate. The aqueous layer was neutralized and acidified to pH 3-4 using 10% citric acid. The product was extracted with ethyl acetate (3×) and washed with brine and dried over sodium sulfate. The solvent was removed to give 3.6 g of 2-(4-(N-(benzyloxycarbonyl)carbamimidoyl)phenylamino)-2-(3-ethoxy-4-isopropoxyphenyl)acetic acid as a yellow solid (80% yield). LC-MS: 506.11 (M+H)+. The enantiomers were separated using a semi-preparative HPLC equipped with an Astex Chirobiotic T column (20 mm×500 mm). The separation was performed using an isocratic method of methanol with 0.1% triethylamine plus 0.2% acetic acid to provide 141F.

Workup

  1. concentrationthe reaction was concentrated
  2. dissolutionredissolved in ethyl acetate
  3. extractionThe product was extracted with ethyl acetate (3×)
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. customThe solvent was removed

Sources & evidence

ORD record
ord-04eb9c31c3de4d42b9aa0ffdc8d88516
Source dataset
uspto-grants-2009_11
Patent number
US07622585B2

Reaction notes

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