Sodium Hydroxide → [1-[(3-iodophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]acetic acid acetate

HRID 1946551Notes

Reaction equation

HRID 1946551 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13]3[CH:14]([C:18](C(OCC)=O)(C(OCC)=O)[C:19]([O:21]CC)=[O:20])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:34]([CH3:36])[CH3:35])[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+]>CO.CCOCC>[C:19]([OH:21])(=[O:20])[CH3:18].[I:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13]3[CH:14]([CH2:18][C:19]([OH:21])=[O:20])[CH2:15][CH2:16][CH2:17][C:12]=3[N:11]=[C:10]2[CH:34]([CH3:36])[CH3:35])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 58460214triethyl [1-[(3-iodophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]methanetricarboxylate

Product 1

HCID 67435457[1-[(3-iodophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-7-yl]acetic acid acetateYield 11.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of Intermediate 92 (7.67 g) in Methanol (150 mL) was added 2M Aqueous Sodium Hydroxide (25.1 mL). The reaction mixture was then stirred at 80° C. and under nitrogen for 17 hours. The reaction mixture was concentrated in vacuo, taken up in glacial acetic acid (28.8 mL) and allowed to stir at 80° C. and under nitrogen for 24 hours. The reaction mixture was concentrated in vacuo to give an orange oily solid. This was suspended in ether, stirred well for 15 mins and then filtered under vacuum. The white solid from this filtration was suspended in ethyl acetate and stirred well at 80° C. for 1.5 hours then filtered under vacuum to give 350 mg of the desired product as an off-white solid. LCMS of the filtrate from the first filtration showed the presence of the desired product as an ethyl ester and so 2M aqueous sodium hydroxide (5 mL) in methanol (5 mL) was added and the mixture left for 2 days. This sample was then loaded in 1:1 methanol:DMSO and purified by column chromatography, reverse phase (C18), using a 5-50% acetonitrile(+0.1% TFA)-water(+0.1% TFA) gradient and a further 80% acetonitrile(+0.1% TFA)-water(+0.1% TFA) gradient. The appropriate fractions were combined, evaporated in vacuo and added to the previously obtained product to give the required product 2.98 g as an off-white solid. LC/MS MH+439, Rt 1.90 min (5 min run).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. stirringto stir at 80° C. and under nitrogen for 24 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customto give an orange oily solid
  5. stirringstirred well for 15 mins
  6. filtrationfiltered under vacuum
  7. filtrationThe white solid from this filtration
  8. stirringstirred well at 80° C. for 1.5 hours
  9. filtrationthen filtered under vacuum

Sources & evidence

ORD record
ord-d231a883240445508d7ea1cc99db7a7b
Source dataset
uspto-grants-2013_03
Patent number
US08399444B2

Reaction notes

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