Sodium Carbonate → 3-((R)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525388Notes

Reaction equation

HRID 525388 reaction equation
FC(F)(F)S(OC1CC[C@@H](N2C(C3C=CC=CC=3)C(C)(C)OC2=O)CC=1)(=O)=O.FC(F)(F)S(OC1CC[C@H](N2C(C3C=CC=CC=3)C(C)(C)OC2=O)CC=1)(=O)=O.FC1C(C2N=CC=CN=2)=CC(B2OC(C)(C)C(C)(C)O2)=CN=1.C(=O)([O-])[O-].[Na+].[Na+].[F:85][C:86]1[N:91]=[CH:90][C:89]([C:92]2[CH2:97][CH2:96][C@H:95]([N:98]3[CH:102]([C:103]4[CH:108]=[CH:107][CH:106]=[CH:105][CH:104]=4)[C:101]([CH3:110])([CH3:109])[O:100][C:99]3=[O:111])[CH2:94][CH:93]=2)=[CH:88][C:87]=1[C:112]1[N:117]=[CH:116][CH:115]=[CH:114][N:113]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[F:85][C:86]1[N:91]=[CH:90][C:89]([C:92]2[CH2:97][CH2:96][C@@H:95]([N:98]3[CH:102]([C:103]4[CH:108]=[CH:107][CH:106]=[CH:105][CH:104]=4)[C:101]([CH3:110])([CH3:109])[O:100][C:99]3=[O:111])[CH2:94][CH:93]=2)=[CH:88][C:87]=1[C:112]1[N:113]=[CH:114][CH:115]=[CH:116][N:117]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 898140903-((S)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-oneHCID 89814340(4R)-4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yl trifluoromethanesulfonateHCID 898151502-(2-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)pyrimidine2×HCID 117857261(4S)-4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yl trifluoromethanesulfonate2×

Product 1

HCID 898137833-((R)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-oneYield 47.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with a mixture of (4R)-4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yl trifluoromethanesulfonate and (4S)-4-(5,5-dimethyl-2-oxo-4-phenyloxazolidin-3-yl)cyclohex-1-en-1-yl trifluoromethanesulfonate (Intermediate M) (730 mg, 1.741 mmol), 2-(2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)pyrimidine (Intermediate H) (577 mg, 1.915 mmol), sodium carbonate (2 M, 2.611 mL, 5.22 mmol), and tetrakis(triphenylphosphine)palladium(0) (201 mg, 0.174 mmol) (commercially available from Strem Chemicals Inc., Newburyport, Mass.). Dioxane (8.703 mL) was added, the system was purged with argon, and the tube was sealed. The mixture was then stirred at 100° C. in the microwave for 1 hour. LC-MS indicated clean and good conversion to the desired product. The reaction mixture was filtered through Celite® brand filter aid and the filtrate was concentrated to afford a yellow oil. The oil was purified using column chromatography on silica gel (RediSep 40 g column, gradient elution with 0 to 60% EtOAc-heptane) to afford a mixture of 3-((S)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one and 3-((R)-4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (370 mg, 0.832 mmol, 47.8% yield) as a white solid. m/z (ESI) 445.2 (M+H)+.

Workup

  1. customthe system was purged with argon
  2. customthe tube was sealed
  3. filtrationThe reaction mixture was filtered through Celite® brand
  4. filtrationfilter aid
  5. concentrationthe filtrate was concentrated
  6. customto afford a yellow oil
  7. customThe oil was purified
  8. customto afford

Sources & evidence

ORD record
ord-481dea022a3643a2b5942e5be35dd76c
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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