1-Butanol → Robenacoxib

HRID 1280845Notes

Reaction equation

HRID 1280845 reaction equation
CN(C)[C:3](=[O:24])[CH2:4][C:5]1[CH:10]=[C:9]([CH2:11][CH3:12])[CH:8]=[CH:7][C:6]=1[NH:13][C:14]1[C:19]([F:20])=[C:18]([F:21])[CH:17]=[C:16]([F:22])[C:15]=1[F:23].[OH-].[Na+].CCCC[OH:32].Cl>C1(C)C=CC=CC=1>[CH2:11]([C:9]1[CH:8]=[CH:7][C:6]([NH:13][C:14]2[C:19]([F:20])=[C:18]([F:21])[CH:17]=[C:16]([F:22])[C:15]=2[F:23])=[C:5]([CH2:4][C:3]([OH:24])=[O:32])[CH:10]=1)[CH3:12]

Participants

6

Reactant 4

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86584268HCID 86584268, compound

Product 1

HCID 6433107Robenacoxib

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

N,N-Dimethyl-5-ethyl-2-(2′,3′,5′,6′-tetrafluoroanilino)phenylacetamide (26 g, 0.073 mol) and 6N NaOH (150 ml) are stirred as a two phase solution with n-BuOH (150 ml) at reflux temperature for 14 hours. After cooling to room temperature, the reaction is poured over ice (500 ml). Toluene (500 ml) is added and the mixture transferred to a separatory funnel. The aqueous phase is brought to a pH of 1 with 3 N HCl. The organic layer is separated and the aqueous phase re-extracted with toluene (250 ml). The combined organic layers are dried (MgSO4) and concentrated under high vacuum (35-50 mbar) on a rotovap taking care not to warm above 50°. Small white needles are obtained by crystallization of the residue from hexane, m.p. 164-166°. Recrystallization from cyclohexane gives 5-ethyl-2-(2′,3′,5′,6′-tetrafluoroanilino)phenylacetic acid a white solid, m.p. 165-169°.

Workup

  1. temperatureat reflux temperature for 14 hours
  2. customthe mixture transferred to a separatory funnel
  3. customThe organic layer is separated
  4. extractionthe aqueous phase re-extracted with toluene (250 ml)
  5. dry with materialThe combined organic layers are dried (MgSO4)
  6. concentrationconcentrated under high vacuum (35-50 mbar) on a rotovap
  7. temperatureto warm above 50°
  8. customSmall white needles are obtained by crystallization of the residue from hexane, m.p. 164-166°
  9. customRecrystallization from cyclohexane

Sources & evidence

ORD record
ord-6f241c1e7a4d4aae97b99bb8db63e315
Source dataset
uspto-grants-2002_09
Patent number
US06451858B2

Reaction notes

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