Cesium carbonate → HCID 86699755, compound

HRID 515188Notes

Reaction equation

HRID 515188 reaction equation
[C:1]([C:3]1[C:8]([CH3:9])=[CH:7][C:6]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:5][C:4]=1OS(C(F)(F)F)(=O)=O)#[N:2].[F:24][C@@H:25]1[CH2:29][CH2:28][NH:27][CH2:26]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:24][C@@H:25]1[CH2:29][CH2:28][N:27]([C:4]2[CH:5]=[C:6]([N:10]3[CH2:11][CH2:12][O:13][CH2:14][CH2:15]3)[CH:7]=[C:8]([CH3:9])[C:3]=2[C:1]#[N:2])[CH2:26]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27591633-FluoropyrrolidineHCID 86699756Trifluoro-methanesulfonic acid (2-cyano-3-methyl-5-morpholin-4-yl-phenyl)ester

Product 1

HCID 86699755HCID 86699755, compoundYield 50.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A solution of affording trifluoro-methanesulfonic acid (2-cyano-3-methyl-5-morpholin-4-yl-phenyl)ester (0.43 g, 1.22 mmol), (3R)-3-fluoro-pyrrolidin (0.19 g, 1.47 mmol) and caesium carbonate (1.6 g, 4.92 mmol) in tetrahydrofuran (25 ml) is degassed and flushed with Argon for 30 min followed by the addition of palladium(II) acetate (6.0 mg, 0.03 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (23 mg, 0.04 mmol). The resulting mixture is stirred at 90° C. for 16 h. After completion of the reaction (monitored by TLC), the mixture is poured onto water (30 ml) and extracted with ethyl acetate (3×50 ml).The combined organic layers are washed with water (2×20 ml), brine (2×20 ml), dried over sodium sulfate and concentrated in vacuo. The crude product is purified by flash column chromatography (silica gel, 15% ethyl acetate/hexane) affording 2-[(3R)-3-fluoro-pyrrolidin-1-yl]-6-methyl-4-morpholin-4-yl-benzonitrile (0.18 g, 0.62 mmol, 50%).

Workup

  1. customflushed with Argon for 30 min
  2. customAfter completion of the reaction (monitored by TLC)
  3. additionthe mixture is poured onto water (30 ml)
  4. extractionextracted with ethyl acetate (3×50 ml).The combined organic layers
  5. washare washed with water (2×20 ml), brine (2×20 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by flash column chromatography (silica gel, 15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d2af3348a5234bbf9c3d523c757a7708
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

Loading…