Cyclopropylboronic acid → HCID 178439237, compound

HRID 505303Notes

Reaction equation

HRID 505303 reaction equation
[F:1][C:2]([F:45])([F:44])[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]([N:26]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:32][CH2:31]4)[CH2:27][CH3:28])=[CH:24][CH:23]=[C:22](Cl)[N:21]=3)[C@H:14]2[CH3:43])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH:46]1(B(O)O)[CH2:48][CH2:47]1>C(=O)([O-])[O-].[K+].[K+].C1COCC1.O>[F:1][C:2]([F:45])([F:44])[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]([N:26]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:32][CH2:31]4)[CH2:27][CH3:28])=[CH:24][CH:23]=[C:22]([C:46]([CH3:48])=[CH2:47])[N:21]=3)[C@H:14]2[CH3:43])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 2

HCID 2760897Cyclopropylboronic acidHCID 178471783HCID 178471783, compound

Product 1

HCID 178439237HCID 178439237, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetate, cyclopropylboronic acid and 1,1′-bis(di-t-butylphosphinoferrocene) palladium dichloride in 1N aqueous potassium carbonate and THF was heated at 85° C. in a sealed tube overnight. The reaction was diluted with water (10 mL) and extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient) to afford 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. Rf=0.44 (20% EtOAc/hexanes). LCMS calc.=670.3; found=670.4 (M+1)+. 1H NMR (600 MHz, CDCl3): δ 7.87 (s, 1 H); 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); 4.96 (d, J=16.7 Hz, 1 H); 4.42-4.36 (m, 2 H); 4.08 (q, J=7.1 Hz, 2 H); 2.98-2.92 (m, 2 H); 2.85 (dd, J=6.5, 13.0 Hz, 1 H); 2.76 (dd, J=7.5, 13.0 Hz, 1H); 2.20 (s, 3 H); 2.12 (d, J=6.8 Hz, 2 H); 1.83-1.65 (m, 5 H); 1.36-1.30 (m, 1 H); 1.22 (t, J=7.1 Hz, 3 H); 0.99 (t, J=7.0 Hz, 3 H); 0.95-0.83 (m, 4 H); 0.72 (d, J=6.7 Hz, 3 H).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. customThis was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-301359cdeeb647b391ffa93adf2e1101
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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