Lithium Hydroxide → 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylic acid

HRID 1508599Notes

Reaction equation

HRID 1508599 reaction equation
[F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([O:42]C)=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([N:45]4[CH:49]=[CH:48][CH:47]=[N:46]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Li+]>C(O)(C(F)(F)F)=O>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([OH:42])=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([N:45]4[CH:49]=[CH:48][CH:47]=[N:46]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:4]=[C:3]([C:2]([F:1])([F:52])[F:51])[CH:8]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86704646methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

Product 1

HCID 569715943'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylic acidYield 82.5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
40 °C

Procedure

To methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (91.4 mg, 0.126 mmol) in dioxanes (2 mL) was added lithium hydroxide (0.5 M, 1.0 mL, 0.505 mmol). The system was heated to 40° C. and was stirred for 1.5 hrs. The reaction was cooled to room temperature and TFA (100 μL) was added to the reaction before volatiles were removed. The crude material was purified by reverse phase HPLC to yield 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-(1H-pyrazol-1-yl)pyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylic acid (86.1 mg, 0.104 mmol). LCMS calc.=711.2. found=711.2. 1H NMR (CD3OD, 500 MHz) δ 8.62 (s, 1H), 7.88 (m, 8H), 7.34 (m, 4H), 6.56 (s, 1H), 5.81 (m, 1H), 4.84 (m, 1H), 4.24 (m, 2H), 3.90 (br s, 3H), 3.36 (br s, 3H), 0.67 (d, J=33.5 Hz, 3H). RTA=14.8 nM

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customwere removed
  3. customThe crude material was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-5fe0103790ba4e688315767a497060ab
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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