Sodium bis(trimethylsilyl)amide → methyl 4'-methoxy-2''-{[(4S,5R)-5-(3-methoxyphenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 607120Notes

Reaction equation

HRID 607120 reaction equation
O[C@H:2]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=1)[C@@H:3]([NH:5][C:6](=[O:15])[O:7]CC1C=CC=CC=1)[CH3:4].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:35][C:36]1[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][C:37]=1[C:46]1[CH:47]=[C:48]([C:54]2[CH:59]=[CH:58][C:57]([C:60]([O:62][CH3:63])=[O:61])=[CH:56][C:55]=2[CH3:64])[CH:49]=[CH:50][C:51]=1[O:52][CH3:53]>CC(N(C)C)=O.C1COCC1>[CH3:53][O:52][C:51]1[CH:50]=[CH:49][C:48]([C:54]2[CH:59]=[CH:58][C:57]([C:60]([O:62][CH3:63])=[O:61])=[CH:56][C:55]=2[CH3:64])=[CH:47][C:46]=1[C:37]1[CH:38]=[CH:39][C:40]([C:42]([F:45])([F:43])[F:44])=[CH:41][C:36]=1[CH2:35][N:5]1[C@@H:3]([CH3:4])[C@@H:2]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=2)[O:7][C:6]1=[O:15]

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 57544358Methyl 2''-(bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylateHCID 86630550benzyl[(1S,2R)-2-hydroxy-2-(3-methoxyphenyl)-1-methylethyl]carbamate

Product 1

HCID 25009504methyl 4'-methoxy-2''-{[(4S,5R)-5-(3-methoxyphenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a 0° C. solution of benzyl [(1S,2R)-2-hydroxy-2-(3-methoxyphenyl)-1-methylethyl]carbamate (40 mg, 0.126 mmol) in DMA (1.5 mL) was added NaHMDS (0.246 mL of a 1M solution in THF, 0.246 mmol). After 5 minutes, a solution of methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (68 mg, 0.138 mmol) in DMA (2.5 mL) was added via cannula. After 5 minutes, the reaction was quenched with saturated NH4Cl solution (10 mL), diluted with EtOAc (20 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (0 to 25% acetone/hexanes), followed by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA) afforded methyl 4′-methoxy-2″-{[(4S,5R)-5-(3-methoxyphenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate. LCMS=644.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 7.94-7.86 (m, 2H), 7.71-7.62 (m, 2H), 7.43-7.36 (m, 2H), 7.31-7.22 (m, 2H), 7.3 (m, 1H), 7.08-7.05 (m, 1H), 6.85-6.83 (m, 1H), 6.75-6.68 (m, 2H), 5.45 (d, J=8.0 Hz), 5.23 (d, J=8.0 Hz), 4.89 (d, J=16.0 Hz), 4.82 (d, J=16.0 Hz), 4.20 (d, J=15.8 Hz), 3.96 (d, J=15.8 Hz), 3.91 (s, 3H), 3.85 (s, 3H), 3.77-3.75 (m, 3H), 3.72-3.69 (m, 1H), 2.31 (s), 2.08 (s), 0.54 (d, J=6.4 Hz), 0.44 (d, J=6.4 Hz).

Workup

  1. waitAfter 5 minutes
  2. customthe reaction was quenched 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. customPurification of the residue by flash chromatography on silica gel (0 to 25% acetone/hexanes)

Sources & evidence

ORD record
ord-a1ffd14e356b4bf28c1da2b5a92043df
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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