Hydrochloric Acid → [5-Bromo-3-methyl-2-(3-trifluoromethoxy-phenyl)-3H-imidazol-4-yl]-[4-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-methanone

HRID 545425Notes

Reaction equation

HRID 545425 reaction equation
[Br:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]([F:17])([F:16])[F:15])[CH:8]=2)[N:4]([CH3:18])[C:3]=1[C:19]([N:21]1[CH2:26][CH2:25][CH:24]([N:27]2[CH2:31][CH2:30][CH2:29][C@H:28]2[CH2:32][O:33]C(=O)C2C=CC=CC=2)[CH2:23][CH2:22]1)=[O:20].BrC1N=C(C2C=CC=C(OC(F)(F)F)C=2)N(C)C=1C(O)=O.N1CCC(N2CCC[C@H]2COC(=O)C2C=CC=CC=2)CC1.[Li+].[OH-].Cl>C1COCC1.CO>[Br:1][C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]([F:17])([F:16])[F:15])[CH:8]=2)[N:4]([CH3:18])[C:3]=1[C:19]([N:21]1[CH2:22][CH2:23][CH:24]([N:27]2[CH2:31][CH2:30][CH2:29][C@H:28]2[CH2:32][OH:33])[CH2:25][CH2:26]1)=[O:20]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 66901590benzoic acid (S)-1-piperidin-4-yl-pyrrolidin-2-ylmethyl ester2×HCID 67133004benzoic acid (S)-1-{1-[5-bromo-3-methyl-2-(3-trifluoromethoxy-phenyl)-3H-imidazole-4-carbonyl]-piperidin-4-yl}-pyrrolidin-2-ylmethyl esterHCID 671331915-bromo-3-methyl-2-(3-trifluoromethoxy-phenyl)-3H-imidazole-4-carboxylic acid

Product 1

HCID 57541123[5-Bromo-3-methyl-2-(3-trifluoromethoxy-phenyl)-3H-imidazol-4-yl]-[4-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-methanone

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of 0.15 g (0.24 mmol) of benzoic acid (S)-1-{1-[5-bromo-3-methyl-2-(3-trifluoromethoxy-phenyl)-3H-imidazole-4-carbonyl]-piperidin-4-yl}-pyrrolidin-2-ylmethyl ester [prepared in analogy to the procedure described for example 2 from 5-bromo-3-methyl-2-(3-trifluoromethoxy-phenyl)-3H-imidazole-4-carboxylic acid (example 72) and benzoic acid (S)-1-piperidin-4-yl-pyrrolidin-2-ylmethyl ester (intermediate 6C)] in 10 ml of THF/MeOH 1:1 was treated with 0.59 ml (0.59 mmol) of a LiOH solution (1.0 molar in H2O) and the mixture was stirred for 20 hours at RT. It was then poured into crashed ice, acidified with HCl (1.0 N) and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 98:2 to 4:1) to give 0.128 g (quant.) of the title compound as colorless amorphous solid. MS: 531.0 (MH+, 1Br).

Workup

  1. additionIt was then poured
  2. extractionextracted twice with EtOAc
  3. washthe organic phases were washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 98:2 to 4:1)

Sources & evidence

ORD record
ord-547d87fc21954aed93587bacb108e3ba
Source dataset
uspto-grants-2011_05
Patent number
US07935707B2

Reaction notes

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