Ammonium Chloride → 2-(3-tert-butyl-5-(ethoxycarbonyl)-1H-pyrazol-1-yl)acetic acid

HRID 1098560Notes

Reaction equation

HRID 1098560 reaction equation
CC(C)([O-])C.[K+].[C:7]([C:11]1[CH:15]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[NH:13][N:12]=1)([CH3:10])([CH3:9])[CH3:8].C([O:25][C:26](=[O:29])[CH2:27]Br)(C)(C)C.[NH4+].[Cl-]>CS(C)=O.C(O)(C(F)(F)F)=O>[C:7]([C:11]1[CH:15]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:13]([CH2:27][C:26]([OH:29])=[O:25])[N:12]=1)([CH3:10])([CH3:8])[CH3:9]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 79177tert-Butyl bromoacetateHCID 2743509Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 206071732-(3-tert-butyl-5-(ethoxycarbonyl)-1H-pyrazol-1-yl)acetic acidYield 100%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Potassium t-butoxide (2.6 g, 23 mmol) was dissolved in DMSO (10 mL) and to this solution was added ethyl 3-tert-butyl-1H-pyrazole-5-carboxylate (4.5 g, 23 mmol) in small portions and stirred under Ar for 15 min. To this solution was added t-butyl-bromoacetate (5.4 g, 28 mmol) slowly at 0° C. with stirring for 45 min at RT. Sat. NH4Cl solution was added and product was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to afford (7.0 g) coupled product as a pasty mass. The above pasty mass was dissolved in TFA (10 mL) and stirred for 3 h at RT. Solvents were removed, water (100 mL) was added and product was extracted with DCM (3×50 ml). The combined organic extracts were washed with brine solution, dried (Na2SO4) and concentrated to yield 2-(3-tert-butyl-5-(ethoxycarbonyl)-1H-pyrazol-1-yl)acetic acid (5.8 gm, 100%) as a pasty mass. 1H NMR (400 MHz, Acetone-d6): δ 6.78 (s, 1H), 5.25 (s, 2H), 4.30 (q, J=7.2 Hz, 2H), 1.35-1.30 (m, 12H); MS (ESI) m/z: 255.2 (M+H+).

Workup

  1. stirringwith stirring for 45 min at RT
  2. extractionproduct was extracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto afford (7.0 g)
  7. stirringstirred for 3 h at RT
  8. customSolvents were removed
  9. additionwater (100 mL) was added
  10. extractionproduct was extracted with DCM (3×50 ml)
  11. washThe combined organic extracts were washed with brine solution
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-05f1e41734e342e8ad8648bafaa7e020
Source dataset
uspto-grants-2012_03
Patent number
US08143293B2

Reaction notes

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