Sodium Hydroxide → HCID 68768115, compound

HRID 1173019Notes

Reaction equation

HRID 1173019 reaction equation
C([O:3][C:4]([C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[C:13]([F:15])[C:12]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:19]=2)=[CH:11][C:10]=1[F:31])=[O:5])C.[OH-].[Na+]>CO>[F:31][C:10]1[CH:11]=[C:12]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:19]=2)[C:13]([F:15])=[CH:14][C:9]=1[C@@H:7]1[CH2:8][C@H:6]1[C:4]([OH:5])=[O:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 131728520HCID 131728520, compound

Product 1

HCID 68768115HCID 68768115, compoundYield 83.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of enantiomerically enriched-(trans)-ethyl-2-[2,5-difluoro-4-({[3-(phenyloxy)phenyl]methyl}amino)phenyl]cyclopropanecarboxylate (III-2g) (0.127 g, 0.30 mmol) and 0.5 mL of 15% aqueous sodium hydroxide in 5 mL of methanol was heated at reflux for 1.5 hours. Methanol was evaporated and the residue was dissolved in water and acidified with concentrated hydrochloric acid. The precipitated product was extracted with dichloromethane, the organic phase washed with water, dried over anhydrous sodium sulfate, and the solvent evaporated to give 0.099 g (83% yield) of the title compound as a white solid. 1 HNMR (400 MHz, CDCl3) δ 7.33 (t, J=8.2 Hz, 2H), 7.31 (t, J=7.8 Hz, 1H), 7.11 (t, J=7.5 Hz, 1H), 7.07 (d, J=7.5 Hz, 2H), 7.00 (d, J=7.8 Hz, 2H), 6.91 (d, J=8.2 Hz, 1H), 6.57 (dd, J=11.8 Hz, 6.7 Hz, 1H), 6.29 (dd, J=11.5 Hz, 7.3 Hz, 1H), 4.30 (s, 2H), 2.59 (m, 1H), 1.78 (m, 1H), 1.59 (m, 1H), 1.33 (m, 1H). ES-MS m/z 394(M-H)+. [α]25,D=+140° (chloroform, c=0.8). Product was determined to be 88% ee by chiral SFC according to Method 1.

Workup

  1. temperatureat reflux for 1.5 hours
  2. customMethanol was evaporated
  3. dissolutionthe residue was dissolved in water
  4. extractionThe precipitated product was extracted with dichloromethane
  5. washthe organic phase washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-b87068fa32314b14b18601aa1b8c5b5b
Source dataset
uspto-grants-2010_11
Patent number
US07834013B2

Reaction notes

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