Acetic Acid → HCID 178439236, compound

HRID 505304Notes

Reaction equation

HRID 505304 reaction equation
[OH-].[K+].[F:3][C:4]([F:49])([F:48])[C:5]1[CH:6]=[C:7]([C@H:15]2[O:19][C:18](=[O:20])[N:17]([CH2:21][C:22]3[C:27]([N:28]([CH2:31][C@H:32]4[CH2:37][CH2:36][C@H:35]([CH2:38][C:39]([O:41]CC)=[O:40])[CH2:34][CH2:33]4)[CH2:29][CH3:30])=[CH:26][CH:25]=[C:24]([C:44]([CH3:46])=[CH2:45])[N:23]=3)[C@H:16]2[CH3:47])[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.Cl.CC(O)=O>CCO.O.[Cl-].[Na+].O>[F:48][C:4]([F:3])([F:49])[C:5]1[CH:6]=[C:7]([C@H:15]2[O:19][C:18](=[O:20])[N:17]([CH2:21][C:22]3[C:27]([N:28]([CH2:31][C@H:32]4[CH2:37][CH2:36][C@H:35]([CH2:38][C:39]([OH:41])=[O:40])[CH2:34][CH2:33]4)[CH2:29][CH3:30])=[CH:26][CH:25]=[C:24]([C:44]([CH3:46])=[CH2:45])[N:23]=3)[C@H:16]2[CH3:47])[CH:8]=[C:9]([C:11]([F:13])([F:14])[F:12])[CH:10]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 178439237HCID 178439237, compound

Product 1

HCID 178439236HCID 178439236, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Aqueous potassium hydroxide (4N, 100 μL) was added to a stirred solution of ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-isopropenylpyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetate (7.3 mg, 0.0109 mmol) in EtOH (0.9 mL) and water (0.35 mL) at room temperature. After 8 h the reaction was acidified to pH 5 with 1 N HCl and then diluted with brine (10 mL). The mixture was extracted with EtOAc (3×20 mL) and the combined extracts were dried (Na2SO4) and concentrated in vacuo to afford the crude product. This was purified by flash chromatography (Si, 12×160 mm, 1% AcOH, 0-65% EtOAc in hexanes gradient) to afford (trans)-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetic acid. Rf=0.59 (1% AcOH, 1:2 EtOAc/hexanes). LCMS calc.=642.3; found=642.2 (M+1)+. 1H NMR (500 MHz, CDCl3): δ 7.87 (s, 1H); 7.78 (s, 2 H); 7.40 (s, 2 H); 5.85 (s, 1 H); 5.75 (d, J=8.6 Hz, 1 H); 5.25 (s, 1 H); 4.97 (d, J=16.7 Hz, 1 H); 4.43-4.35 (m, 2 H); 2.98-2.90 (m, 2 H); 2.84 (dd, J=8.5, 12.9 Hz, 1 H); 2.76 (dd, J=7.4, 12.9 Hz, 1 H); 2.20 (br s, 5 H); 1.80-1.64 (m, 5 H); 1.35-1.24 (m, 1 H); 0.99 (t, J=7.0 Hz, 3 H); 0.95-0.83 (m, 4 H); 0.72 (d, J=6.6 Hz, 3 H).

Workup

  1. extractionThe mixture was extracted with EtOAc (3×20 mL)
  2. dry with materialthe combined extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customto afford the crude product
  5. customThis was purified by flash chromatography (Si, 12×160 mm, 1% AcOH, 0-65% EtOAc in hexanes gradient)
  6. customto afford (trans)-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetic acid

Sources & evidence

ORD record
ord-29f0578d157642a789add7fa4bf37314
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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