Potassium tert-butoxide → methyl 4'-methoxy-2''-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 538000Notes

Reaction equation

HRID 538000 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C@H:9]1[O:14][C:13](=[O:15])[NH:12][CH2:11][CH2:10]1.[CH3:16]C([O-])(C)C.[K+].Br[CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:35]=[C:36]([C:42]2[CH:47]=[CH:46][C:45]([C:48]([O-:50])=[O:49])=[CH:44][C:43]=2[CH3:51])[CH:37]=[CH:38][C:39]=1[O:40][CH3:41]>CN(C=O)C>[CH3:41][O:40][C:39]1[CH:38]=[CH:37][C:36]([C:42]2[CH:47]=[CH:46][C:45]([C:48]([O:50][CH3:16])=[O:49])=[CH:44][C:43]=2[CH3:51])=[CH:35][C:34]=1[C:25]1[CH:26]=[CH:27][C:28]([C:30]([F:32])([F:33])[F:31])=[CH:29][C:24]=1[CH2:23][N:12]1[CH2:11][CH2:10][C@@H:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[O:14][C:13]1=[O:15]

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 68997782(6S)-6-(2-methoxyphenyl) 1,3-oxazinan-2-oneHCID 866261472''-(Bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 24740082methyl 4'-methoxy-2''-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (6S)-6-(2-methoxyphenyl)-1,3-oxazinan-2-one (31.6 mg, 0.152 mmol) in DMF (1.5 mL) was added t-BuOK (16.5 mg, 0.144 mmol). The reaction was stirred for 15 minutes, then a solution of 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (75 mg, 0.152 mmol) in DMF (15 mL) was added via cannula. The reaction was stirred at room temperature for 1 hour, and then quenched with saturated NH4Cl solution (10 mL), diluted with EtOAc (20 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (10 to 50% EtOAc/hexanes) to afford methyl 4′-methoxy-2″-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate LCMS=619.8 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 7.78-7.94 (m, 2H), 7.68 (s, 1H), 7.60 (t, J=9.0 Hz, 1H), 7.25-7.44 (m, 5H), 6.79-7.15 (m, 4H), 5.58 (dd, J=9.2, 2.5 Hz), 5.32 (dd, J=9.2, 2.5 Hz), 4.76 (d, J=15.3 Hz, 1H), 4.57 (d, J=15.3 Hz), 4.48 (d, J=15.6 Hz), 3.92 (s, 3H), 3.86 (s), 3.84 (s), 3.80 (s), 3.65 (s), 2.88-3.16 (m, 2H), 2.35 (s), 2.32 (s), 1.85-2.20 (m, 2H).

Workup

  1. stirringThe reaction was stirred at room temperature for 1 hour
  2. customquenched with saturated NH4Cl solution (10 mL)
  3. additiondiluted with EtOAc (20 mL)
  4. washwashed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (10 to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5759c8a148a843ffa2c347f4284d6b18
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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