(Methoxycarbonylsulfamoyl)triethylammonium hydroxide → 2-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-4-phenyl-4,5-dihydro-1,3-oxazole

HRID 2400581Notes

Reaction equation

HRID 2400581 reaction equation
O[CH2:2][C@H:3]([NH:10][C:11]([C:13]1[CH:17]=[C:16]([CH3:18])[N:15]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[N:14]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[OH-].C(NS([N+](CC)(CC)CC)(=O)=O)(OC)=O>C1COCC1.O>[CH3:18][C:16]1[N:15]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=2)[N:14]=[C:13]([C:11]2[O:12][CH2:2][CH:3]([C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=3)[N:10]=2)[CH:17]=1

Participants

5

Reactant 2

HCID 11032497(Methoxycarbonylsulfamoyl)triethylammonium hydroxideHCID 59504667N-[(1R)-2-Hydroxy-1-phenylethyl]-5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxamide

Product 1

HCID 595047302-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-4-phenyl-4,5-dihydro-1,3-oxazoleYield 69.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of N-[(1R)-2-hydroxy-1-phenylethyl]-5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxamide (Step 1, 350 mg, 1.0 mmol) and carbomethoxysulfamoyltriethylammonium hydroxide inner salt (Burgess' reagent, 310 mg, 1.03 mmol) in THF (20 mL) was heated at 70° C. for 1 h. After being cooled to rt, the mixture was diluted with water (10 mL), and the organic phase was extracted with ethyl acetate (1×25 mL), washed with brine (1×25 mL), dried (Na2SO4), filtered, and concentrated to dryness. The crude was then purified with an ISCO CombiFlash Companion using gradient elution from 0% to 20% EtOAc in hexanes to afford the title compound as a yellow oil (230 mg, 69%): 1H NMR (300 MHz, DMSO-d6) δ 7.31-7.34 (m, 2H), 7.24-7.28 (m, 3H), 7.12 (d, 2H), 7.01 (d, 2H), 6.52 (s, 1H), 5.27-5.32 (m, 1H), 5.29 (s, 2H), 4.69-4.75 (m, 1H), 4.06-4.12 (m, 1H), 2.25 (s, 3H), 2.22 (s, 3H); ES-MS m/z 332.20, HPLC RT (Method B) 3.20 min.

Workup

  1. temperatureAfter being cooled to rt
  2. extractionthe organic phase was extracted with ethyl acetate (1×25 mL)
  3. washwashed with brine (1×25 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude was then purified with an ISCO CombiFlash Companion
  8. washelution from 0% to 20% EtOAc in hexanes

Sources & evidence

ORD record
ord-0fbea5a592174f209eca541833fd5f5c
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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