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

HRID 2386698Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-{4-chloro-3-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-propyl]-phenoxymethyl}-benzoic acid ethyl ester (Example 1, 83 mg) in tetrahydrofuran (0.3 ml) and methanol (0.3 ml) was added a 1 M aqueous LiOH solution (0.29 ml) at 0° C. The mixture was stirred at 0° C. for 30 min and at room temperature for 5.5 h. The mixture was cooled in an ice bath and acidified using 1 M aqueous HCl. The mixture was concentrated to dryness. The product was purified by chromatography (SiO2, CH2Cl2/MeOH 1:0=>85:15) to give the title compound (49 mg) as colorless foam. MS (m/e, ISP neg. ion)=548.2 [M−H+].

Workup

temperatureThe mixture was cooled in an ice bath
concentrationThe mixture was concentrated to dryness
customThe product was purified by chromatography (SiO2, CH2Cl2/MeOH 1:0=>85:15)

Sources & evidence

ORD record: ord-1525a1c85de040a88393424d70752fb4
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08268820B2

Reaction notes

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