Potassium tert-butoxide → 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

HRID 538002Notes

Reaction equation

HRID 538002 reaction equation
Br[CH2:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[CH:14]=[C:15]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][C:22]=2[CH3:31])[CH:16]=[CH:17][C:18]=1[O:19][CH3:20].[F:32][C:33]([F:53])([F:52])[C:34]1[CH:35]=[C:36]([C@H:44]2[O:49][C:48](=[O:50])[NH:47][C@@H:46]([CH3:51])[CH2:45]2)[CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1.CC(C)([O-])C.[K+]>CN(C=O)C>[F:53][C:33]([F:32])([F:52])[C:34]1[CH:35]=[C:36]([C@H:44]2[O:49][C:48](=[O:50])[N:47]([CH2:2][C:3]3[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=3[C:13]3[CH:14]=[C:15]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][C:22]=4[CH3:31])[CH:16]=[CH:17][C:18]=3[O:19][CH3:20])[C@@H:46]([CH3:51])[CH2:45]2)[CH:37]=[C:38]([C:40]([F:41])([F:42])[F:43])[CH:39]=1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 57544358Methyl 2''-(bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylateHCID 57544409(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazinan-2-one

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (78.5 mg; 0.159 mmol) and (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazinan-2-one (43.4 mg; 0-133 mmol) in DMF (1 mL) was added potassium tert-butoxide (14.9 mg; 0.133 mmol). The reaction was stirred at room temperature for 2 h, quenched with sat. NH4Cl, and partitioned between EtOAc (10 mL) and sat. NH4Cl (10 mL). The aqueous layer was extracted with EtOAc (4×25 mL) and the combined extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-100% EtOAc/hexanes gradient) to afford 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 as a colorless glass. LCMS=740.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers) δ 7.89-7.82 (m, 3H), 7.71-7.66 (m, 2H), 7.59 (s, 1H), 7.43 (d, J=8.5 Hz, 1H), 7.41-7.38 (m, 1H), 7.30 (d, J=8 Hz, 1H), 7.22 (d, J=2.2 Hz, 1H), 7.16 (d, J=8 Hz, 1H) 7.11-7.07 (m, 1H), 5.38 (d, J=15.6 Hz, 1H), 4.65 (d, J=11.5 Hz, 1H), 4.32 (d, J=15.8 Hz, 1H), 3.93 (s, 3H), 3.92 (s, 3H), 3.30-3.25 (m, 1H), 2.34 (s, 3H), 2.17-2.12 (m, 1H), 1.73-1.65 (m, 1H), 1.08 (d, J=6.2 Hz, 3).

Workup

  1. customquenched with sat. NH4Cl
  2. custompartitioned between EtOAc (10 mL) and sat. NH4Cl (10 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (4×25 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 flash silica gel chromatography (0-100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-9d4532717c204d5d8eeaed3433644f89
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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