Methanol → 2-(5-(2-chloropyridin-4-yl)-2-methyl-3-(2-(phenylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetic acid

HRID 1189546Notes

Reaction equation

HRID 1189546 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]([CH2:13][C:14]([O:16]CC3C=CC=CC=3)=[O:15])[C:11]([CH3:24])=[C:10]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[S:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)(=[O:34])=[O:33])[CH:9]=2)[CH:5]=[CH:4][N:3]=1.CO.O.[OH-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]([CH2:13][C:14]([OH:16])=[O:15])[C:11]([CH3:24])=[C:10]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[S:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)(=[O:33])=[O:34])[CH:9]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium HydroxideHCID 53245778HCID 53245778, compound

Product 1

HCID 532457792-(5-(2-chloropyridin-4-yl)-2-methyl-3-(2-(phenylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetic acidYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of crude benzyl 2-(5-(2-chloropyridin-4-yl)-2-methyl-3-(2-(phenylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (514 mg, 0.360 mmol, contaminated with ˜60% 2-(phenylsulfonyl)phenyl)methanol) in tetrahydrofuran (4 mL) and water (4 mL) was added a 3M solution of aqueous sodium hydroxide (28.8 mg, 0.720 mmol). The reaction turned yellow upon addition of the base solution, and the reaction was stirred at room temperature for 20 minutes after which LCMS analysis indicated that the saponification was complete. The reaction was concentrated to remove the THF, and then diluted in water and washed with dichloromethane (2×50 mL) and ethyl acetate (1×50 mL). The water layer was acidified to pH=4 with 3M aqueous hydrochloric acid solution. The product was extracted with ethyl acetate and washed with a brined aqueous layer (3×50 mL), dried (sodium sulfate), filtered and concentrated to a yellow solid. A significant loss of product was observed. In order to recover additional product, the aqueous layer prior to the final extraction was further acidified and re-extracted with ethyl acetate (3×50 mL), dried (sodium sulfate), filtered and concentrated. The batches were combined to afford 2-(5-(2-chloropyridin-4-yl)-2-methyl-3-(2-(phenylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetic acid as a yellow solid (99.5 mg, 0.207 mmol, 58% yield). 1H NMR (400 MHz, CDCl3): δ (ppm) 8.31 (d, 1H), 8.27 (d, 1H), 7.85 (m, 2H), 7.40-7.56 (m, 5H), 7.13-7.16 (m, 2H), 7.04 (d, 1H), 5.85 (s, 1H), 4.64 (s, 2H), 4.05 (s, 2H), 2.00 (s, 3H).

Workup

  1. additionThe reaction turned yellow upon addition of the base solution
  2. concentrationThe reaction was concentrated
  3. customto remove the THF
  4. additiondiluted in water
  5. washwashed with dichloromethane (2×50 mL) and ethyl acetate (1×50 mL)
  6. extractionThe product was extracted with ethyl acetate
  7. washwashed with a brined aqueous layer (3×50 mL)
  8. dry with materialdried (sodium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated to a yellow solid
  11. customIn order to recover additional product
  12. extractionthe aqueous layer prior to the final extraction
  13. extractionre-extracted with ethyl acetate (3×50 mL)
  14. dry with materialdried (sodium sulfate)
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-ac6609de1035476eb9800fb1cf19b67b
Source dataset
uspto-grants-2014_03
Patent number
US08674115B2

Reaction notes

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