Cesium carbonate → HCID 59271805, compound

HRID 1893200Notes

Reaction equation

HRID 1893200 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:40])[CH:9]([C:20]1[N:25]=[C:24]([C:26]([O:28][CH3:29])=[O:27])[C:23]([O:30][S:31]([CH3:34])(=[O:33])=[O:32])=[C:22]([O:35]S(C)(=O)=O)[N:21]=1)[CH2:10][CH2:11][CH2:12][CH:13](OS(C)(=O)=O)[CH3:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].CS(Cl)(=O)=O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH3:40])[C@@H:9]1[CH2:10][CH2:11][CH2:12][C@@H:13]([CH3:14])[N:21]2[C:22](=[O:35])[C:23]([O:30][S:31]([CH3:34])(=[O:32])=[O:33])=[C:24]([C:26]([O:28][CH3:29])=[O:27])[N:25]=[C:20]12)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 31297Methanesulfonyl chlorideHCID 59271884HCID 59271884, compound

Product 1

HCID 59271805HCID 59271805, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of the methyl 2-{1-[(tert-butoxycarbonyl)(methyl)amino]-5-[(methylsulfonyl)oxy]hexyl}-5,6-bis[(methylsulfonyl)oxy]pyrimidine-4-carboxylate (62 g, 98 mmol) and cesium carbonate (64 g, 196 mmol) in DMF (400 mL) was heated at 100° C. overnight. The reaction mixture was cooled to room temperature and then cooled further to 0° C. More cesium carbonate (60 g) was added followed by MsCl (10 mL) and stirring continued for 1 hour. The reaction mixture was filtered to remove solids and the solids were then washed with methylene chloride until the filtrate ran clear. The filtrate was then stripped and finally under high vacuum at 35° C. to remove the DMF. The thick dark red residual sludge was diluted with ether and filtered. The filter cake was washed with ether. The resulting cream colored solid was dissolved in methylene chloride and washed once with cold half-saturated brine and the solution dried over sodium sulfate. Filtration and concentration gave the racemic trans diastereomer as determined by NMR and LC-MS: 1H NMR (400 MHz, CDCl3) δ 5.74 (m, 1H), 5.41 (dd, J=1.6, 13.5 Hz, 1H), 3.92 (s, 3H), 3.50 (s, 3H), 2.95 (s, 3H), 1.60-2.94 (m, 6H), 1.57 (d, J=7.3 Hz, 3H), 1.44 (s, 9H). ES MS M+1=460.12.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperaturecooled further to 0° C
  3. filtrationThe reaction mixture was filtered
  4. customto remove solids
  5. washthe solids were then washed with methylene chloride until the filtrate
  6. customwas then stripped and finally under high vacuum at 35° C.
  7. customto remove the DMF
  8. additionThe thick dark red residual sludge was diluted with ether
  9. filtrationfiltered
  10. washThe filter cake was washed with ether
  11. dissolutionwas dissolved in methylene chloride
  12. washwashed once with cold half-saturated brine
  13. dry with materialthe solution dried over sodium sulfate
  14. filtrationFiltration and concentration
  15. customgave the racemic trans diastereomer

Sources & evidence

ORD record
ord-674dbcd637f34540b51ffd33fb1c48e4
Source dataset
uspto-grants-2013_08
Patent number
US08513234B2

Reaction notes

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