Methanol → (3-{3-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-5-methyl-pyridin-2-yl}-4-methoxy-phenyl)-acetic acid

HRID 389268Notes

Reaction equation

HRID 389268 reaction equation
C([O:3][C:4](=[O:30])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([C:14]2[C:19]([CH2:20][N:21]([C:24]([CH:26]3[CH2:28][CH2:27]3)=[O:25])[CH2:22][CH3:23])=[CH:18][C:17]([CH3:29])=[CH:16][N:15]=2)[CH:7]=1)C.[Li+].[OH-].CO>C1COCC1>[CH:26]1([C:24]([N:21]([CH2:20][C:19]2[C:14]([C:8]3[CH:7]=[C:6]([CH2:5][C:4]([OH:30])=[O:3])[CH:11]=[CH:10][C:9]=3[O:12][CH3:13])=[N:15][CH:16]=[C:17]([CH3:29])[CH:18]=2)[CH2:22][CH3:23])=[O:25])[CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 58579952(3-{3-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-5-methyl-pyridin-2-yl}-4-methoxy-phenyl)-acetic acid ethyl ester

Product 1

HCID 45255230(3-{3-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-5-methyl-pyridin-2-yl}-4-methoxy-phenyl)-acetic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To (3-{3-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-5-methyl-pyridin-2-yl}-4-methoxy-phenyl)-acetic acid ethyl ester (0.154 g, 0.38 mmol) in THF (1.5 mL) was added 1N aqueous LiOH (1.14 mL, 1.14 mmol), and enough MeOH to clarify the solution. The reaction was stirred at 40° C. for 30 minutes, until no starting material was seen by analytical tlc. The mixture was concentrated, diluted with H2O, and washed twice with EtOAc. After filtering through a 25 μM nylon filter, the aqueous layer was acidified to pH 3 with 1N aqueous HCl, and the volume was reduced by half and then saturated with NH4Cl. The mixture was extracted five times with CH2Cl2, and then the aqueous layer was concentrated to leave residual salts and a trace of liquid, which was further extracted with CH2Cl2 until only a small amount of the desired product remained in the salts. The combined organic layers were dried over Na2SO4, filtered, and concentrated to give the title compound.

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with H2O
  3. washwashed twice with EtOAc
  4. filtrationAfter filtering through a 25 μM nylon
  5. filtrationfilter
  6. extractionThe mixture was extracted five times with CH2Cl2
  7. concentrationthe aqueous layer was concentrated
  8. customto leave residual salts
  9. extractiona trace of liquid, which was further extracted with CH2Cl2 until only a small amount of the desired product
  10. dry with materialThe combined organic layers were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-fa706bd7d4a9409b8842dc154688a203
Source dataset
uspto-grants-2013_02
Patent number
US08378107B2

Reaction notes

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