Hydrochloric Acid → HCID 24755052, compound

HRID 268640Notes

Reaction equation

HRID 268640 reaction equation
Cl.CCOC(C)=O.[C:8]([O:12][C:13](=[O:47])[CH2:14][CH:15]([OH:46])[CH2:16][CH:17]([OH:45])[CH:18]=[CH:19][C:20]1[N:21]([C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)[N:22]=[C:23]([C:28](=[O:37])[NH:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:24]=1[CH:25]([CH3:27])[CH3:26])([CH3:11])([CH3:10])[CH3:9]>CO.[Pd]>[C:8]([O:12][C:13](=[O:47])[CH2:14][C@H:15]([OH:46])[CH2:16][C@H:17]([OH:45])[CH2:18][CH2:19][C:20]1[N:21]([C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)[N:22]=[C:23]([C:28](=[O:37])[NH:29][CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:24]=1[CH:25]([CH3:27])[CH3:26])([CH3:10])([CH3:11])[CH3:9]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 68800922HCID 68800922, compound2×

Product 1

HCID 24755052HCID 24755052, compoundYield 61.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Conditions

Temperature
25 °C

Procedure

To a solution of (6-{2-[5-benzylcarbamoyl-2-(4-fluoro-phenyl)-4-isopropyl-2H-pyrazol-3-yl}-2,2-dimethyl-[1,3]dioxan-4-yl)-acetic acid tert-butyl ester (0.360 g, 0.61 mmol) in MeOH (20 mL) was added 1N HCl (2 mL) and the solution was stirred for 3 hrs at 25° C. Subsequently, the reaction solvent was removed under reduced pressure and ethyl acetate (50 mL) and saturated NaHCO3 (10 mL) were added. The organic layer was separated, washed with brine, dried (Na2SO4) and concentrated to afford, after silica gel chromatography (35% EtOAc/Hex), 7-[5-benzylcarbamoyl-2-(4-fluoro-phenyl)-4-isopropyl-2H-pyrazol-3-yl]-3,5-dihydroxy-hept-6-enoic acid tert-butyl ester (0.231 g, 69%). Subsequently, to a solution of 7-[5-benzylcarbamoyl-2-(4-fluoro-phenyl)-4-isopropyl-2H-pyrazol-3-yl]-3,5-dihydroxy-hept-6-enoic acid tert-butyl ester (0.241 g, 0.437 mmol) in MeOH (20 mL) was added 10% Pd-C (50 mg; commercially available from Sigma Aldrich), and the reaction vessel was evacuated and filled with hydrogen gas (via balloon) for 3 hours. The reaction mixture was then filtered through a pad of celite and to the filtrate was added The crude product was purified by silica gel chromatography (30-50% EtOAc/Hex) to provide (3R,5R)-7-[5-benzylcarbamoyl-2-(4-fluoro-phenyl)-4-isopropyl-2H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic acid tert-butyl ester (0.143 g, 59%): MS(APCI+): m/z554.3 (M+H).

Workup

  1. customSubsequently, the reaction solvent was removed under reduced pressure and ethyl acetate (50 mL) and saturated NaHCO3 (10 mL)
  2. additionwere added
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customto afford
  8. customcommercially available from Sigma Aldrich), and the reaction vessel was evacuated
  9. additionfilled with hydrogen gas (via balloon) for 3 hours
  10. filtrationThe reaction mixture was then filtered through a pad of celite and to the filtrate
  11. additionwas added The crude product
  12. customwas purified by silica gel chromatography (30-50% EtOAc/Hex)

Sources & evidence

ORD record
ord-1b133ae3785f48fb83000ff9c62a8f0e
Source dataset
uspto-grants-2008_11
Patent number
US07446121B2

Reaction notes

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