Hydrochloric Acid → HCID 89813901, compound

HRID 525396Notes

Reaction equation

HRID 525396 reaction equation
F[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@@H:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:17]([CH3:26])([CH3:25])[O:16][C:15]3=[O:27])[CH2:10][CH:9]=2)=[CH:4][C:3]=1[C:28]1[N:33]=[CH:32][CH:31]=[CH:30][N:29]=1.[O:34]1CCOCC1.Cl>O>[CH3:25][C:17]1([CH3:26])[O:16][C:15](=[O:27])[N:14]([CH:11]2[CH2:12][CH2:13][C:8]([C:5]3[CH:4]=[C:3]([C:28]4[N:33]=[CH:32][CH:31]=[CH:30][N:29]=4)[C:2](=[O:34])[NH:7][CH:6]=3)=[CH:9][CH2:10]2)[C@H:18]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 89813923HCID 89813923, compound

Product 1

HCID 89813901HCID 89813901, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A resealable tube was charged with (4S)-3-(4-(6-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (See Step 1 in the synthesis of Examples 72 and 73)(50 mg, 0.112 mmol, 50% ee), dioxane (2.647 mL), and water (882 μL). Concentrated HCl (37%) (221 μL) was added, the system was flushed with argon, and the tube was sealed. The reaction mixture was then stirred at 100° C. for 2 hours. LC-MS indicated a clean and complete reaction. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution. The aqueous phase was extracted with EtOAc. The organic phase was concentrated under reduced pressure. The material thus obtained was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 100% MeOH in DCM. The resulting product was then washed with 10% ammonium hydroxide in MeOH. The solution was concentrated under reduced pressure providing (4S)-5,5-dimethyl-3-(4-(6-oxo-5-(pyrimidin-2-yl)-1,6-dihydropyridin-3-yl)cyclohex-3-en-1-yl)-4-phenyloxazolidin-2-one (44 mg, 0.099 mmol, 88% yield, 50% ee) as yellow solid. m/z (ESI) 443.1 (M+H)+.

Workup

  1. customthe system was flushed with argon
  2. customthe tube was sealed
  3. customcomplete reaction
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution
  6. extractionThe aqueous phase was extracted with EtOAc
  7. concentrationThe organic phase was concentrated under reduced pressure
  8. customThe material thus obtained
  9. customwas absorbed onto a plug of silica gel
  10. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  11. washeluting with a gradient of 0% to 100% MeOH in DCM
  12. washThe resulting product was then washed with 10% ammonium hydroxide in MeOH
  13. concentrationThe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-84fe6f15636448c8bf843857f012807b
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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