Hydrochloric Acid → (R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid

HRID 644034Notes

Reaction equation

HRID 644034 reaction equation
[CH:1]1([C@H:7]2[N:12]3[CH:13]=[C:14]([C:19](C(F)(F)F)=[O:20])[C:15]4[CH:16]=[CH:17][CH:18]=[C:10]([C:11]=43)[O:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-:25].[Na+].Cl>O1CCOCC1>[CH:1]1([C@H:7]2[N:12]3[CH:13]=[C:14]([C:19]([OH:25])=[O:20])[C:15]4[CH:16]=[CH:17][CH:18]=[C:10]([C:11]=43)[O:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68676699(R)-3-cyclohexyl-6-trifluoromethylcarbonyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine

Product 1

HCID 68675192(R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-3-cyclohexyl-6-trifluoromethylcarbonyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine (628 mg, 1.86 mmol) in 1,4-dioxane (20 ml) was added 4 N NaOH (5.0 ml). The mixture was refluxed for 42 h, then acidified to pH 1 using 5 N hydrochloric acid and partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane, and combined organic layers were washed with brine, dried over Na2SO4 and concentrated to afford (R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (572 mg). The title compound was prepared following the method of Example 7, using (R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid amide (prepared from (R)-3-cyclohexyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid) instead of 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carboxylic acid amide. EsIMS: m/z 411.0 [M+H]+; [α]D22−30.7° (c=1.50 mg/ml in chloroform)

Workup

  1. temperatureThe mixture was refluxed for 42 h
  2. custompartitioned between dichloromethane and water
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washwere washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-de625e0d13d44f90979906e500590520
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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