Acetic Acid → 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoic acid

HRID 1508565Notes

Reaction equation

HRID 1508565 reaction equation
[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8]([C:33]3[CH:34]=[C:35]([CH2:41][CH2:42][C:43]([O:45]C)=[O:44])[CH:36]=[CH:37][C:38]=3[O:39][CH3:40])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[OH-].[Li+].C(O)(=O)C>O1CCOCC1.O.C(OCC)(=O)C>[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:19]=[C:20]([C:28]([F:30])([F:29])[F:31])[CH:21]=[C:22]([C:24]([F:25])([F:27])[F:26])[CH:23]=4)[O:14][C:13]3=[O:32])[C:8]([C:33]3[CH:34]=[C:35]([CH2:41][CH2:42][C:43]([OH:45])=[O:44])[CH:36]=[CH:37][C:38]=3[O:39][CH3:40])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 3939Lithium HydroxideHCID 56968291methyl 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoate

Product 1

HCID 569711453-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoate (93 mg, 0.143 mmol) was dissolved in dioxane (2 mL) and water (0.5 mL). As the solution was stirred vigorously, 1M lithium hydroxide (0.285 mL, 0.285 mmol) was added dropwise. The reaction was stirred at room temperature for 1 hr and then quenched with acetic acid (0.020 mL, 0.357 mmol). The reaction was diluted with ethyl acetate (15 mL) and washed with water (2×10 mL) and brine (10 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was redissolved in dichloromethane (2 mL) and heptanes (2 mL) and concentrated again. Purification of the residue by flash chromatography on silica gel (0 to 100% ethyl acetate/hexanes) afforded 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoic acid. LCMS=638.2 (M+H)+. 1H NMR (CDCl3, 500 MHz) δ 7.85 (s, 1H), 7.72 (s, 2H), 7.30 (d, J=8.7 Hz, 1H), 7.17 (dd, J=8.4, 2.2 Hz, 1H), 7.00 (bs, 1H), 6.87 (d, J=8.4 Hz, 1H), 6.27 (d, J=8.3 Hz, 1H), 5.61 (bs, 1H), 4.8-4.4 (m, 2H), 4.07 (m, 4H), 3.85 (m, 1H), 3.75 (s, 3H), 2.92 (m, 2H), 2.64 (m, 2H), 2.41 (m, 2H), 0.75-0.58 (m, 3H).

Workup

  1. stirringThe reaction was stirred at room temperature for 1 hr
  2. washwashed with water (2×10 mL) and brine (10 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was redissolved in dichloromethane (2 mL)
  7. concentrationheptanes (2 mL) and concentrated again
  8. customPurification of the residue by flash chromatography on silica gel (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9b308c7a6e11462ba9773271c2b5f59a
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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