Sodium Hydroxide → HCID 25006310, compound

HRID 1799370Notes

Reaction equation

HRID 1799370 reaction equation
[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:23]3[CH:28]=[CH:27][C:26]([CH2:29][C:30]([O:32]C)=[O:31])=[CH:25][CH:24]=3)[C:18]=1[S:19][CH2:20][CH2:21][CH3:22])=[O:13])[CH2:8]2.[OH-].[Na+]>CO>[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12]([C:14]1[CH:15]=[N:16][N:17]([C:23]3[CH:24]=[CH:25][C:26]([CH2:29][C:30]([OH:32])=[O:31])=[CH:27][CH:28]=3)[C:18]=1[S:19][CH2:20][CH2:21][CH3:22])=[O:13])[CH2:8]2

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59516151HCID 59516151, compound2×

Product 1

HCID 25006310HCID 25006310, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 2-[4-[4-(2-adamantylcarbamoyl)-5-propylsulfanyl-pyrazol-1-yl]phenyl]acetate (Intermediate #34) (220 mg, 0.47 mmol) was dissolved in methanol (10 mL) and treated at ambient temperature with a 2M solution of sodium hydroxide (1.17 mL, 2.35 mmol). The mixture was stirred overnight and then methanol was removed by evaporation under reduced pressure. The clear aqueous solution was diluted with water (20 mL) and acidified to pH3 with 2M HCl. The resulting white precipitate was extracted into ethyl acetate (2×20 mL). The combined extracts were washed with brine (10 mL), dried (MgSO4) and evaporated to give the crude product. The crude product was purified by preparative HPLC using decreasingly polar mixtures of water (containing 0.1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-[4-[4-(2-adamantylcarbamoyl)-5-propylsulfanyl-pyrazol-1-yl]phenyl]acetic acid (66 mg, 31%).

Workup

  1. custommethanol was removed by evaporation under reduced pressure
  2. additionThe clear aqueous solution was diluted with water (20 mL)
  3. extractionThe resulting white precipitate was extracted into ethyl acetate (2×20 mL)
  4. washThe combined extracts were washed with brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give the crude product
  8. customThe crude product was purified by preparative HPLC
  9. additionFractions containing the desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-ae2bbb3d967e4b079198de5200b5685a
Source dataset
uspto-grants-2013_01
Patent number
US08344016B2

Reaction notes

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