Sodium hydride → 2''-({5-[3,5-Bis(trifluoromethyl)phenyl]-4,4-dimethyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

HRID 607123Notes

Reaction equation

HRID 607123 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:13]([OH:28])[C:14]([NH:17][C:18](=[O:27])OCC2C=CC=CC=2)([CH3:16])[CH3:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].Br[CH2:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=1[C:45]1[CH:46]=[C:47]([C:53]2[CH:58]=[CH:57][C:56]([C:59]([O:61]C)=[O:60])=[CH:55][C:54]=2[CH3:63])[CH:48]=[CH:49][C:50]=1[O:51][CH3:52]>C1COCC1>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:13]2[O:28][C:18](=[O:27])[N:17]([CH2:34][C:35]3[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=3[C:45]3[CH:46]=[C:47]([C:53]4[CH:58]=[CH:57][C:56]([C:59]([OH:61])=[O:60])=[CH:55][C:54]=4[CH3:63])[CH:48]=[CH:49][C:50]=3[O:51][CH3:52])[C:14]2([CH3:16])[CH3:15])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 53363830Benzyl {2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1,1-dimethylethyl}carbamateHCID 57544358Methyl 2''-(bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Product 1

HCID 250098732''-({5-[3,5-Bis(trifluoromethyl)phenyl]-4,4-dimethyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzyl {2-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-1,1-dimethylethyl}carbamate (65 mg, 0.149 mmol) in THF (1.5 mL) was added NaH (13 mg, 0.542 mmol) and methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (91.1 mg, 0.185 mmol). The reaction was stirred for 72 hours, and then additional NaH (36.2 mg, 1.51 mmol) was added. After 6 more hours at room temperature, the reaction was quenched with saturated NH4Cl solution (10 mL) and diluted with EtOAc (20 mL). The aqueous layer was extracted with EtOAc (20 mL), and the combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA) afforded 2″-({5-[3,5-bis(trifluoromethyl)phenyl]-4,4-dimethyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS=726.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) a 8.03-8.02 (m, 1H), 7.80-7.96 (m, 1H), 7.89 (s, 1H), 7.79-7.76 (m, 2H), 7.62-7.59 (m, 1H), 7.42-7.31 (m, 3H), 7.22-7.08 (m, 3H), 5.26-5.28 (m, 1H), 4.81 (d, J=16.6 Hz), 4.44-4.42 (m, 1H), 4.02 (d, J=16.6 Hz), 3.85 (s, 3H), 2.37-2.35 (m, 3H), 1.24 (s), 1.06 (s), 0.56-0.54 (m, 3H).

Workup

  1. customAfter 6 more hours at room temperature, the reaction was quenched with saturated NH4Cl solution (10 mL)
  2. additiondiluted with EtOAc (20 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  4. washthe combined organic extracts were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA)

Sources & evidence

ORD record
ord-a95d7f5752c04ec9a4a89fc59393d47b
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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