Potassium Hydroxide → 2''-({(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazinan-3-yl}methyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

HRID 538003Notes

Reaction equation

HRID 538003 reaction equation
[F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=3[C:31]3[CH:32]=[C:33]([C:39]4[CH:44]=[CH:43][C:42]([C:45]([O:47]C)=[O:46])=[CH:41][C:40]=4[CH3:49])[CH:34]=[CH:35][C:36]=3[O:37][CH3:38])[C@@H:15]([CH3:50])[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+]>CO>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=3[C:31]3[CH:32]=[C:33]([C:39]4[CH:44]=[CH:43][C:42]([C:45]([OH:47])=[O:46])=[CH:41][C:40]=4[CH3:49])[CH:34]=[CH:35][C:36]=3[O:37][CH3:38])[C@@H:15]([CH3:50])[CH2:14]2)[CH:4]=[C:3]([C:2]([F:1])([F:52])[F:51])[CH:8]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 86626148methyl 2''-({(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazinan-3-yl}methyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 247376892''-({(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazinan-3-yl}methyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of methyl 2″-({(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazinan-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (Step A; 48 mg; 0.065 mmol) in MeOH (5 mL), was added 4 M KOH (800 μL). The reaction was stirred at room temperature for 4 h, quenched with saturated citric acid and partitioned between EtOAc (25 mL) and water (25 mL). The aqueous layer was extracted with EtOAc (3×25 mL) and the combined extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by preparatory thin layer chromatography, eluting with 2:1 hexanes:EtOAc+1% AcOH to afford 2″-({(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazinan-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid as a white solid. LCMS=725.9 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers) δ 7.97-7.94 (m, 1H), 7.86-7.82 (m, 2H), 7.78 (d, J=8 Hz, 1H), 7.68-7.66 (m, 1H), 7.63-7.61 (m, 1H), 7.45-7.39 (m, 2H), 7.34 (d, J=8 Hz, 1H), 7.25-7.20 (m, 2H), 7.12-7.09 (m, 1H), 5.37 (d, J=15.5 Hz, 1H), 4.67 (d, J=11.4 Hz, 1H), 4.34 (d, J=15.6 Hz, 1H), 3.91 (s, 3H), 3.32-3.26 (m, 1H), 2.36 (s, 3H), 2.19-2.13 (m, 1H), 1.75-1.67 (m, 1H), 1.09 (d, J=6.1 Hz, 3H).

Workup

  1. customquenched with saturated citric acid
  2. custompartitioned between EtOAc (25 mL) and water (25 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (3×25 mL)
  4. washthe combined extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparatory thin layer chromatography
  9. washeluting with 2:1 hexanes

Sources & evidence

ORD record
ord-637465e18f894134975ed035147a4e15
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

Loading…