Cesium carbonate → HCID 67983240, compound

HRID 1748216Notes

Reaction equation

HRID 1748216 reaction equation
[CH:1]12[NH:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH:3]([O:9][CH2:10][C:11]1[C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][C:26]([F:29])([F:28])[F:27])=[N:13][O:14][C:15]=1[CH:16]1[CH2:18][CH2:17]1)[CH2:2]2.CC(N(C)C)=O.[F:36][C:37]1[CH:38]=[C:39]([CH:44]=[CH:45][C:46]=1F)[C:40]([O:42][CH3:43])=[O:41].C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.O>[CH:16]1([C:15]2[O:14][N:13]=[C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][C:26]([F:28])([F:27])[F:29])[C:11]=2[CH2:10][O:9][CH:3]2[CH2:2][CH:1]3[N:8]([C:46]4[CH:45]=[CH:44][C:39]([C:40]([O:42][CH3:43])=[O:41])=[CH:38][C:37]=4[F:36])[CH:5]([CH2:6][CH2:7]3)[CH2:4]2)[CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 31374DimethylacetamideHCID 2775358Methyl 3,4-difluorobenzoateHCID 67983256HCID 67983256, compound

Product 1

HCID 67983240HCID 67983240, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

The amine, 4-((8-azabicyclo[3.2.1]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole (41.5 mg, 0.102 mmol), dimethylacetamide (0.6 mL), methyl 3,4 difluorobenzoate (510 mg, 3.0 mmol), and cesium carbonate (108 mg, 0.33 mmol) were combined sequentially and heated to 100° C. for about 20 minutes and then 120° C. for approximately 1 hour. The mixture was diluted with ethyl acetate 20 mL and water washed (2×3 mL). The organics were dried under vacuum to a residue, the resulting residue was diluted with 3 mL of MeOH, and the liquid was directly purified using mass directed reverse phase HPLC under a gradient of 30 to 90% acetonitrile/water that was TFA modified (0.05%). The resulting product was cold vacuum concentrated and free based using an SPE polymer support cartridge and MeOH (5 mL) mobilizing solvent (product SPE PLHCO3 MP part no PL3540-C603). All resulting methanol effluent was concentrated to give the free based intermediate ester as a dense oil.

Workup

  1. washwashed (2×3 mL)
  2. customThe organics were dried under vacuum to a residue
  3. additionthe resulting residue was diluted with 3 mL of MeOH
  4. customthe liquid was directly purified
  5. concentrationconcentrated
  6. concentrationAll resulting methanol effluent was concentrated
  7. customto give the

Sources & evidence

ORD record
ord-dc46c77778954972b41497e1d9329d25
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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