Cesium carbonate → HCID 67282035, compound

HRID 1482783Notes

Reaction equation

HRID 1482783 reaction equation
C([O:4][CH2:5][C@@H:6]1[CH2:8][C@:7]1([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=1)[CH2:9][O:10]S(C1C=CC(C)=CC=1)(=O)=O)(=O)C.[CH3:28][C:29]1[N:34]=[C:33]([CH3:35])[C:32](O)=[CH:31][N:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Na+]>C(#N)C.CC(OC)(C)C.CCOC(C)=O.CCCCCCC>[CH3:28][C:29]1[N:34]=[C:33]([CH3:35])[C:32]([O:10][CH2:9][C@@:7]2([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)[CH2:8][C@H:6]2[CH2:5][OH:4])=[CH:31][N:30]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 450800822,4-Dimethylpyrimidin-5-olHCID 71715593HCID 71715593, compound

Product 1

HCID 67282035HCID 67282035, compound

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolventHCID 21899848Ethylacetate heptaneSolvent2×

Conditions

Temperature
67.5 °C

Procedure

((1R,2S)-2-(3-fluorophenyl)-2-((tosyloxy)methyl)cyclopropyl)methyl acetate (8, 11.05 g, 0.028 mol, 1.0 equiv.), 2,4-dimethylpyrimidin-5-ol (3.74 g, 0.030 mol, 1.07 equiv.), and cesium carbonate (22.94 g, 1.8 equiv.) were dissolved in ACN (110.5 mL), under nitrogen. The solution was stirred vigorously and heated to 65-70° C. for 2-3 hours. The reaction was monitored by HPLC and TLC (EtOAc/Heptane=1/1). Once complete, aqueous 1 N NaOH solution (71.82 mL) was added to the reaction mixture. The reaction mixture was stirred at 20-25° C. for 10-16 h, and was monitored by HPLC and TLC (EtOAc/Heptane=1/1). Once the hydrolysis reaction was complete, the reaction mixture was diluted with MTBE (110.50 mL) and stirred for at least 15 min. The aqueous layer was back extracted once with MTBE (55.25 mL). The organic layers were combined and washed once with saturated aqueous NaCl solution (33.15 mL), The solvent was removed under reduced pressure to afford the title compound; ((1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)cyclopropyl)methanol: (11, 8.51 g).

Workup

  1. stirringThe reaction mixture was stirred at 20-25° C. for 10-16 h
  2. customOnce the hydrolysis reaction
  3. stirringstirred for at least 15 min
  4. extractionThe aqueous layer was back extracted once with MTBE (55.25 mL)
  5. washwashed once with saturated aqueous NaCl solution (33.15 mL)
  6. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-b69a3b1f863947b29eb5ea14fc80fa18
Source dataset
uspto-grants-2016_08
Patent number
US09416109B2

Reaction notes

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