Sodium Hydroxide → 1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylic acid

HRID 255383Notes

Reaction equation

HRID 255383 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1/[CH:9]=[CH:10]/[CH2:11][N:12]1[CH2:17][CH2:16][C@H:15]([CH2:18][CH2:19][CH2:20][N:21]2[C:26]3[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=[CH:30][C:25]=3[O:24][CH2:23][C:22]2=[O:33])[C@H:14]([C:34]([O:36]C)=[O:35])[CH2:13]1.[OH-].[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1/[CH:9]=[CH:10]/[CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([CH2:18][CH2:19][CH2:20][N:21]2[C:26]3[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=[CH:30][C:25]=3[O:24][CH2:23][C:22]2=[O:33])[CH:14]([C:34]([OH:36])=[O:35])[CH2:13]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86642666Methyl cis(+/-)1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate

Product 1

HCID 866426651-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylic acidYield 20.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

A solution of methyl Cis(±)-1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-methoxy-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate (Example 123) (105 mg, 0.204 mmol) in methanol (1 mL) was treated with a solution of sodium hydroxide (1N, 1 mL) the reaction was warmed to 30° C. for 18 hours. The temperature was increased to 60° C. for 6 hours. The solvents were evaporated, the reaction was diluted with ethyl acetate and water. The pH was adjusted to 7 with 1N HCl. The layers were separated. The aqueous phase was extracted with ethyl acetate (2×20mL). The organic layers were combined dried over magnesium sulfate and concentrated at reduced pressure. The residue was taken up and dichloromethane and precipitated with ether in a dry ice/acetone bath. The solvent was decanted. The solid was dried under high vacuum to obtain 21 mg (20%) of an off-white solid.

Workup

  1. temperatureThe temperature was increased to 60° C. for 6 hours
  2. customThe solvents were evaporated
  3. additionthe reaction was diluted with ethyl acetate and water
  4. customThe layers were separated
  5. extractionThe aqueous phase was extracted with ethyl acetate (2×20mL)
  6. dry with materialThe organic layers were combined dried over magnesium sulfate
  7. concentrationconcentrated at reduced pressure
  8. customdichloromethane and precipitated with ether in a dry ice/acetone bath
  9. customThe solvent was decanted
  10. customThe solid was dried under high vacuum

Sources & evidence

ORD record
ord-3461e0cfda46407b9cf442cbf9734fed
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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