Hydrochloric Acid → 2''-{[(4S,5R)-5-(3-chloro-4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

HRID 2093227Notes

Reaction equation

HRID 2093227 reaction equation
C([O:8][C:9](=[O:23])[NH:10][C@@H:11]([CH3:22])[C@@H:12]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=1)O)C1C=CC=CC=1.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]C)=[O:61])=[CH:56][C:55]=2[CH3:64])[CH:49]=[CH:50][C:51]=1[O:52][CH3:53].[OH-].[Na+].Cl>CC(N(C)C)=O.C1COCC1>[Cl:21][C:16]1[CH:15]=[C:14]([C@H:12]2[O:23][C:9](=[O:8])[N:10]([CH2:35][C:36]3[CH:41]=[C:40]([C:42]([F:43])([F:44])[F:45])[CH:39]=[CH:38][C:37]=3[C:46]3[CH:47]=[C:48]([C:54]4[CH:59]=[CH:58][C:57]([C:60]([OH:62])=[O:61])=[CH:56][C:55]=4[CH3:64])[CH:49]=[CH:50][C:51]=3[O:52][CH3:53])[C@H:11]2[CH3:22])[CH:19]=[CH:18][C:17]=1[F:20]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 57544358Methyl 2''-(bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylateHCID 86630551benzyl[(1S,2R)-2-(3-chloro-4-fluorophenyl)-2-hydroxy-1-methylethyl]carbamate

Product 1

HCID 250098722''-{[(4S,5R)-5-(3-chloro-4-fluorophenyl)-4-methyl-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 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a 0° C. solution of benzyl[(1S,2R)-2-(3-chloro-4-fluorophenyl)-2-hydroxy-1-methylethyl]carbamate (51.4 mg, 0.152 mmol) in DMA (1.5 mL) was added NaHMDS (0.296 mL of a 1M solution in THF, 0.296 mmol). After 5 minutes, a solution of methyl 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (75 mg, 0.152 mmol) in DMA (2.5 mL) was added via cannula. After 5 minutes, saturated aqueous NaOH solution (3 mL) was added, and the mixture was allowed to warm to room temperature. After 3 hours, the mixture was acidified with 6 N HCl and concentrated. The residue was purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA) to afford 2″-{[(4S,5R)-5-(3-chloro-4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid. LCMS=627.9 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 7.95-7.62 (m, 2H), 7.69-7.52 (m, 2H), 7.43-7.37 (m, 2H), 7.30-7.24 (m, 1H), 7.18-7.11 (m, 2H), 7.08-6.86 (m, 3H), 5.44 (d, J=8.0 Hz), 5.18 (d, J=8.0 Hz), 4.92-4.85 (m, 1H), 4.18 (d, J=15.5), 3.96 (d, J=15.5), 3.93-3.85 (m, 3H), 3.73-3.66 (m, 1H), 2.36 (s), 2.32 (s), 0.55 (d, J=6.6 Hz), 0.44 (d, J=6.6 Hz).

Workup

  1. waitAfter 5 minutes
  2. waitAfter 3 hours
  3. concentrationconcentrated
  4. customThe residue was purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA)

Sources & evidence

ORD record
ord-dea31904cf774685b91da5ab9e8461cb
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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