Potassium Bromide → HCID 72187942, compound

HRID 515174Notes

Reaction equation

HRID 515174 reaction equation
FC1C=CC([N:8]([CH3:32])[C:9]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:13][C:12]=2OS(C(F)(F)F)(=O)=O)=[O:10])=CC=1.[F-:33].[K+].[Br-].[K+].[CH:37]1(B(O)O)[CH2:39][CH2:38]1>C1(C)C=CC=CC=1>[F:33][C:11]1[CH:16]=[CH:15][C:14]([CH2:32][NH:8][C:9](=[O:10])[C:11]2[C:16]([CH3:17])=[CH:15][C:14]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:13][C:12]=2[CH:37]2[CH2:39][CH2:38]2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 253877Potassium BromideHCID 522689Potassium FluorideHCID 2760897Cyclopropylboronic acidHCID 86699743HCID 86699743, compound

Product 1

HCID 72187942HCID 72187942, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of trifluoro-methanesulfonic acid [2-[(4-fluorophenyl)-methyl-carbamoyl]-3-methyl-5-morpholin-4-yl-phenyl]ester (synthesized according to the methods described in sections a) to d) of example 17) (0.16 g, 0.34 mmol), potassium fluoride (0.08 g, 1.41 mmol), potassium bromide (0.05 g, 0.40 mmol) and cyclopropylboronic acid (0.06 g, 0.67 mmol) in dry toluene (3 ml) is degassed and flushed with argon for 20 min. To the reaction mixture is added tetrakis(triphenylphosphin)palladium(0) (0.039 g, 0.033 mmol) and subjected to microwave irradiation at 120° C. for 1 h. The reaction mixture is poured onto ice and extracted with ethyl acetate (3×30 ml). The combined organic layers are washed with water (20 ml), brine (20 ml) and dried over sodium sulfate. The solvent is evaporated to get the crude product. The reaction is repeated once and the combined fractions are purified by column chromatography (silica gel, 20% ethyl acetate/hexane) followed by preparative HPLC to afford N-[(4-fluorophenyl)-methyl]-2-cyclopropyl-6-methyl-4-morpholin-4-yl-benzamide (example 18) (0.12 g, 0.32 mmol, 28%). [M+H]+ 369.2.

Workup

  1. customis degassed
  2. customflushed with argon for 20 min
  3. customirradiation at 120° C. for 1 h
  4. additionThe reaction mixture is poured onto ice
  5. extractionextracted with ethyl acetate (3×30 ml)
  6. washThe combined organic layers are washed with water (20 ml), brine (20 ml)
  7. dry with materialdried over sodium sulfate
  8. customThe solvent is evaporated
  9. customto get the crude product
  10. customthe combined fractions are purified by column chromatography (silica gel, 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-3866a946e1fe4bc78efa1c2b8ad949c7
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

Loading…