Tetrahydrofuran → Fevipiprant

HRID 1254886Notes

Reaction equation

HRID 1254886 reaction equation
C[O:2][C:3](=[O:30])[CH2:4][C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][C:16]=2[C:25]([F:28])([F:27])[F:26])[C:6]=1[CH3:29].C1COCC1.[OH-].[Na+]>O>[CH3:24][S:21]([C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:7]2[C:8]3=[N:9][CH:10]=[CH:11][CH:12]=[C:13]3[C:5]([CH2:4][C:3]([OH:30])=[O:2])=[C:6]2[CH3:29])=[C:16]([C:25]([F:28])([F:27])[F:26])[CH:17]=1)(=[O:22])=[O:23]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 67219460methyl 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate

Product 1

HCID 23582412Fevipiprant

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture comprising [1-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid methyl ester: (11.8 g, 26.8 mmol) in water (100 ml) and THF (250 ml) is added dropwise NaOH (53.6 ml of a 1M aqueous solution) at room temperature and the two phase suspension is allowed to stir overnight. The solvent is removed in vacuo and the crude is triturated with diethyl ether, DCM and ethyl acetate. The resulting solid is dissolved in hot water (150 ml) and adjusted to pH 3-4 using 6M HCl. The suspension that forms is filtered and is further purified by dissolving in hot IPA (250 ml) and refluxing in the presence of charcoal for 5 minutes. The solution is filtered and the titled product is recrystallised from water/IPA as a white/pale green crystals. (MH+ 427)

Workup

  1. customThe solvent is removed in vacuo
  2. customthe crude is triturated with diethyl ether, DCM and ethyl acetate
  3. dissolutionThe resulting solid is dissolved in hot water (150 ml)
  4. filtrationThe suspension that forms is filtered
  5. customis further purified
  6. dissolutionby dissolving in hot IPA (250 ml)
  7. temperaturerefluxing in the presence of charcoal for 5 minutes
  8. filtrationThe solution is filtered
  9. customthe titled product is recrystallised from water/IPA as a white/pale green crystals

Sources & evidence

ORD record
ord-4f96091504a5434e9491d5f212ab14ba
Source dataset
uspto-grants-2013_06
Patent number
US08455645B2

Reaction notes

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