Hydrochloric Acid → 5-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-propyl]-phenoxy}-2-fluoro-benzoic acid

HRID 2096771

Reaction equation

HRID 2096771 reaction equation
C([O:3][C:4](=[O:40])[C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:37])[C:19]([OH:36])([C:24]3[CH:25]=[CH:26][C:27]4[O:32][CH2:31][C:30](=[O:33])[N:29]([CH3:34])[C:28]=4[CH:35]=3)[C:20]([F:23])([F:22])[F:21])=[C:14]([Cl:38])[CH:13]=2)[CH:8]=[CH:7][C:6]=1[F:39])C.[Li+].[OH-].Cl>O1CCCC1.CO>[Cl:38][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[CH:18]([CH3:37])[C:19]([OH:36])([C:24]1[CH:25]=[CH:26][C:27]2[O:32][CH2:31][C:30](=[O:33])[N:29]([CH3:34])[C:28]=2[CH:35]=1)[C:20]([F:22])([F:21])[F:23])[O:11][C:9]1[CH:8]=[CH:7][C:6]([F:39])=[C:5]([CH:10]=1)[C:4]([OH:40])=[O:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 666973435-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-propyl]-phenoxy}-2-fluoro-benzoic acid ethyl ester

Product 1

HCID 469091285-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-propyl]-phenoxy}-2-fluoro-benzoic acidYield 81.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-{3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-propyl]-phenoxy}-2-fluoro-benzoic acid ethyl ester (23 mg, 0.04 mmol) in tetrahydrofuran (0.085 ml) and methanol (0.085 ml) was added a 1 M aqueous LiOH solution (0.08 ml, 0.08 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min and at room temperature for 2.5 h. The mixture was cooled in an ice bath and acidified using 1 M aqueous HCl. The mixture was concentrated. To the residue, water was added, extracted twice with AcOEt, the organic phases were washed with water, dried (MgSO4) and concentrated to give the title compound (18 mg) as a white solid. MS (m/e, ISP neg. ion)=552.2 [M−H+].

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. concentrationThe mixture was concentrated
  3. additionTo the residue, water was added
  4. extractionextracted twice with AcOEt
  5. washthe organic phases were washed with water
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3bc13da47d7b4364b24bda98649dbc46
Source dataset
uspto-grants-2013_05
Patent number
US08450313B2

Linked notes

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