Methanol → HCID 66937385, compound

HRID 538163Notes

Reaction equation

HRID 538163 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:15]([CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21])[C:14]3[CH:22]=[C:23]([S:30][CH2:31][CH3:32])[C:24]([C:26]([F:29])([F:28])[F:27])=[CH:25][C:13]=3[N:12]=2)[CH:10]=1)=[O:5])[CH3:2].CO.[OH:35]OS([O-])=O.[K+].S([O-])(O[O-])(=O)=O.[K+].[K+]>O.CCOC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:15]([CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21])[C:14]3[CH:22]=[C:23]([S:30]([CH2:31][CH3:32])=[O:35])[C:24]([C:26]([F:29])([F:27])[F:28])=[CH:25][C:13]=3[N:12]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 10313463Potassium peroxymonosulphateHCID 23707502Potassium hydroxy sulfiteHCID 66937162HCID 66937162, compound

Product 1

HCID 66937385HCID 66937385, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

To a mixture of 1-[1-(2-methoxy-ethoxymethyl)-6-ethylsulfanyl-5-trifluoromethyl-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (EXAMPLE 95, product from Step A) (0.501 g, 1.14 mmol) and methanol (5.7 mL) was added a solution of Oxone®/potassium peroxymonosulfate (1.47 g, 2.40 mmol) in water (5.7 mL). The mixture was stirred for 44 h at 23° C. EtOAc (50 mL) and water (30 mL) were added and the biphasic mixture was stirred. The layers were separated and the aqueous layer was further extracted with EtOAc (50 mL). The combined organic layers were washed with brine, dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (10-80% EtOAc/hexanes) to yield the tiled compound (0.260 g, 48% yield, 5:2 mixture of regioisomers) and 1-[1-(2-methoxy-ethoxymethyl)-6-ethylsulfinyl-5-trifluoromethyl-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.232 g, 45% yield, 2:1 mixture of regioisomers). MS (ESI/CI): mass calcd. for C13H23ClN4O6S, 470.1; m/z found, 471.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.91 (d, J=0.6 Hz, 1H), 8.53 (s, 1H), 8.20 (d, J=0.6 Hz, 1H), 7.82 (s, 1H), 6.21 (s, 2H), 4.37 (q, J=7.1 Hz, 2H), 3.72-3.67 (m, 2H), 3.53-3.42 (m, 4H), 3.29 (s, 3H), 1.39 (t, J=7.1 Hz, 3H), 1.30 (t, J=7.4 Hz, 3H).

Workup

  1. stirringthe biphasic mixture was stirred
  2. customThe layers were separated
  3. extractionthe aqueous layer was further extracted with EtOAc (50 mL)
  4. washThe combined organic layers were washed with brine
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified (FCC) (10-80% EtOAc/hexanes)
  9. customto yield

Sources & evidence

ORD record
ord-b5a3f3a8088a486abbd28f8ad258f0d3
Source dataset
uspto-grants-2014_10
Patent number
US08865713B2

Reaction notes

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