Potassium Hydroxide → HCID 46220481, compound

HRID 2094641Notes

Reaction equation

HRID 2094641 reaction equation
Cl[C:2]([F:12])([F:11])C(C1C=CC=CC=1)=O.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([C:41]2[CH:50]=[CH:49][C:48]3[C:43](=[CH:44][CH:45]=[C:46]([OH:51])[CH:47]=3)[CH:42]=2)[C@@H:21]([C:25]2[CH:40]=[CH:39][C:28]([C:29]([NH:31][CH2:32][CH2:33][C:34]([O:36]CC)=[O:35])=[O:30])=[CH:27][CH:26]=2)[CH2:22][CH2:23][CH3:24])=[CH:16][CH:15]=1.[OH-].[K+]>C(#N)C>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([C:41]2[CH:50]=[CH:49][C:48]3[C:43](=[CH:44][CH:45]=[C:46]([O:51][CH:2]([F:12])[F:11])[CH:47]=3)[CH:42]=2)[C@@H:21]([C:25]2[CH:40]=[CH:39][C:28]([C:29]([NH:31][CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[O:30])=[CH:27][CH:26]=2)[CH2:22][CH2:23][CH3:24])=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 2382962-Chloro-2,2-difluoroacetophenoneHCID 58468277HCID 58468277, compound

Product 1

HCID 46220481HCID 46220481, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Chlorodifluroacetophenone (294 mg, 1.54 mmol) was added to a mixture of ethyl N-(4-{(1S)-1-[(4-chlorophenyl)(6-hydroxy-2-naphthyl)methyl]butyl}benzoyl)-β-alaninate (140 mg, 0.257 mmol), KOH (303 mg, 5.40 mmol), and acetonitrile (3.0 mL) at −78° C., then the resulting mixture was warmed to 80° C. and stirred for 3 hours. The mixture was cooled to RT, quenched with 2.0 N HCl (aq), then diluted with EtOAc. The organic layer was washed twice with water then concentrated. The residue was purified by preparative reverse phase HPLC, eluting with water/MeCN+0.1% TFA to afford the title compound. 1H NMR (500 MHz, CD3OD): δ 7.68 (d, J=9.0 Hz, 1H), 7.64 (s, 1H), 7.58-7.49 (m, 5H), 7.42 (d, J=8.7 Hz, 1H), 7.37-7.29 (m, 5H), 7.16-7.12 (m, 1H), 6.82 (t, J 7.4 Hz, 1H), 4.39 (d, J=11.8 Hz, 1H), 3.76-3.67 (m, 1H), 3.53-3.47 (m, 2H), 2.56-2.50 (m, 2H), 1.59 (d, J=8.9 Hz, 2H), 1.07 (d, J=10.2 Hz, 2H), 0.79 (t, J=7.2 Hz, 3H); LC2 2.49 min. [M+H]+ 566.

Workup

  1. temperatureThe mixture was cooled to RT
  2. customquenched with 2.0 N HCl (aq)
  3. additiondiluted with EtOAc
  4. washThe organic layer was washed twice with water
  5. concentrationthen concentrated
  6. customThe residue was purified by preparative reverse phase HPLC
  7. washeluting with water/MeCN+0.1% TFA

Sources & evidence

ORD record
ord-5dea33445f84426eb4dd1fd13a813739
Source dataset
uspto-grants-2013_05
Patent number
US08445538B2

Reaction notes

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