Methanol → HCID 66937482, compound

HRID 538167Notes

Reaction equation

HRID 538167 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][CH3:31])[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:34]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]([CH3:31])=[O:34])[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 66937087HCID 66937087, compound

Product 1

HCID 66937482HCID 66937482, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

To a mixture of 1-[1-(2-methoxy-ethoxymethyl)-6-methylsulfanyl-5-trifluoromethyl-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (Intermediate from EXAMPLE 71, product from Step B) (0.300 g, 0.654 mmol) and methanol (3.3 mL) was added a solution of OXONE®/potassium peroxymonosulfate (0.402 g, 0.654 mmol) in water (3.3 mL). The mixture was allowed to stir for 4 h at 23° C. EtOAc (40 mL) and water (20 mL) were added and the biphasic mixture was stirred. The layers were separated and the aqueous layer was further extracted with EtOAc (30 mL). The combined organic layers were washed with brine (15 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (20-100% EtOAc/hexanes) to yield the titled compound (0.249 g, 80% yield) as a 10:9 mixture of regioisomers. MS (ESI/CI): mass calcd. for C19H21F3N4O5S, 474.1; m/z found, 475.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.94 (d, J=0.6 Hz, 1H), 8.58 (s, 1H), 8.22 (s, 1H), 8.08 (s, 1H), 6.34-6.23 (m, 2H), 4.38 (q, J=7.1 Hz, 2H), 3.74-3.66 (m, 2H), 3.51-3.41 (m, 2H), 3.28 (s, 3H), 2.81 (s, 3H), 1.40 (t, J=7.1 Hz, 3H).

Workup

  1. stirringthe biphasic mixture was stirred
  2. customThe layers were separated
  3. extractionthe aqueous layer was further extracted with EtOAc (30 mL)
  4. washThe combined organic layers were washed with brine (15 mL)
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified (FCC) (20-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6cbe5562f7604f7eba52cd7e386f34dc
Source dataset
uspto-grants-2014_10
Patent number
US08865713B2

Reaction notes

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