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

HRID 255296Notes

Reaction equation

HRID 255296 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][CH:15]([CH2:18][CH2:19][CH2:20][N:21]2[C:26]3[CH:27]=[C:28]([C:31]#[N:32])[CH:29]=[CH:30][C:25]=3[O:24][CH2:23][C:22]2=[O:33])[CH:14]([C:34]([O:36]C)=[O:35])[CH2:13]1.[OH-].[Na+].Cl>CO.O>[C:31]([C:28]1[CH:29]=[CH:30][C:25]2[O:24][CH2:23][C:22](=[O:33])[N:21]([CH2:20][CH2:19][CH2:18][CH:15]3[CH2:16][CH2:17][N:12]([CH2:11]/[CH:10]=[CH:9]/[C:3]4[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=4[F:1])[CH2:13][CH:14]3[C:34]([OH:36])=[O:35])[C:26]=2[CH:27]=1)#[N:32]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 15982403Methyl 1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate

Product 1

HCID 159824044-[3-(6-Cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]-1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]piperidine-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of methyl 1-[(2E)-3-(2,5-difluorophenyl)prop-2-en-1-yl]-4H-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate (Example 64) (73 mg, 0.143 mmol) in methanol (12 mL) and water (5 mL) was treated with sodium hydroxide solution (1N, 1 mL). After 64 hours, the pH was adjusted to 6 with 1N HCl. The mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over magnesium sulfate and concentrated at reduced pressure. Chromatography on silica gel using methanol in dichloromethane (0-10%) and trituration with diethyl ether gave the title compound as a colorless solid, mixture of diastereomers, 10 mg (14%).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  2. dry with materialThe combined organic extracts were dried over magnesium sulfate
  3. concentrationconcentrated at reduced pressure
  4. customgave

Sources & evidence

ORD record
ord-0b81f5977a22455f9045299eb4e10241
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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