Trifluoroacetic anhydride → (1S,2R)-2,2,2-Trifluoro-N-[4'-(2-hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-biphenyl-3-yl]-N-methylacetamide

HRID 380032Notes

Reaction equation

HRID 380032 reaction equation
[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1.Br[C:24]1[CH:25]=[C:26]([N:30]([CH3:37])[C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])[CH:27]=[CH:28][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(O)C.ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:33][C:32]([F:34])([F:35])[C:31]([N:30]([C:26]1[CH:27]=[C:28]([C:8]2[CH:9]=[CH:10][C:5]([O:4][C@@H:3]([CH3:14])[C@H:2]([OH:1])[CH2:15][CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:6][CH:7]=2)[CH:29]=[CH:24][CH:25]=1)[CH3:37])=[O:36]

Participants

8

Reactant 4

HCID 9845Trifluoroacetic anhydrideHCID 10340Sodium CarbonateHCID 18367627N-(3-bromo-phenyl)-2,2,2-trifluoro-N-methylacetamideHCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid

Product 1

HCID 54477561(1S,2R)-2,2,2-Trifluoro-N-[4'-(2-hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-biphenyl-3-yl]-N-methylacetamideYield 64.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.150 g, Example 33), N-(3-bromo-phenyl)-2,2,2-trifluoro-N-methylacetamide (0.282 g), 2M aqueous sodium carbonate (0.50 ml) and tetrakis(triphenylphosphine)palladium (0) (0.020 g) in ethanol (3 ml) with heating at 90° C. for 2 hours. After work up, the residue was purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane. The product obtained was dissolved in dichloromethane (3 ml), and cooled to 0° C. Trifluoroacetic anhydride (0.09 ml) was added dropwise, the reaction mixture stirred for 1 hour at room temperature, before concentrating under reduced pressure. Methanol (10 ml) and water (10 ml) were added and the resulting mixture was stirred for 30 minutes at room temperature. The product was extracted with ethyl acetate, and the combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as an oil (0.148 g).

Workup

  1. customPrepared
  2. customAfter work up, the residue was purified by normal-phase HPLC
  3. washeluting with a gradient of 0-25% ethanol in dichloromethane
  4. customThe product obtained
  5. temperaturecooled to 0° C
  6. concentrationbefore concentrating under reduced pressure
  7. additionMethanol (10 ml) and water (10 ml) were added
  8. stirringthe resulting mixture was stirred for 30 minutes at room temperature
  9. extractionThe product was extracted with ethyl acetate
  10. dry with materialthe combined extracts were dried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1aaedea0b35a44cdbeeb712058c6d551
Source dataset
uspto-grants-2001_10
Patent number
US06300352B1

Reaction notes

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