Potassium Carbonate → 1,1-Dimethylethyl 4-{[3-({[(6-fluoro-3'-formyl-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl}-1-piperidinecarboxylate

HRID 2080347Notes

Reaction equation

HRID 2080347 reaction equation
B(O)O.Br[C:5]1[CH:6]=[C:7]([CH2:12][NH:13][C:14]([C:16]2[CH:17]=[C:18]([CH2:22][CH:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)[CH:19]=[CH:20][CH:21]=2)=[O:15])[CH:8]=[CH:9][C:10]=1[F:11].[C:36]([O-:39])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.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:11][C:10]1[C:5]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([CH:36]=[O:39])[CH:10]=2)=[CH:6][C:7]([CH2:12][NH:13][C:14]([C:16]2[CH:17]=[C:18]([CH2:22][CH:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)[CH:19]=[CH:20][CH:21]=2)=[O:15])=[CH:8][CH:9]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 577367091,1-Dimethylethyl 4-{[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]methyl)-1-piperidinecarboxylate

Product 1

HCID 577366931,1-Dimethylethyl 4-{[3-({[(6-fluoro-3'-formyl-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl}-1-piperidinecarboxylateYield 161.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-formylphenyl)boronic acid (21 mg, 0.14 mmol) in dioxane (3 mL) and water (1 mL) was added 1,1-dimethylethyl 4-{[3-({[(3-bromo-4-fluorophenyl)methyl]amino}carbonyl)phenyl]methyl)-1-piperidinecarboxylate (70 mg, 0.14 mmol), K2CO3 (97 mg, 0.7 mmol) and Pd(PPh3)4 (8 mg, 0.007 mmol). The resulting solution was irradiated in a microwave reactor at 150° C. for 20 minutes then diluted with EtOAc (5 mL). The organic layer was separated and the aqueous layer was further extracted by EtOAc (2×5 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by Gilson HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 90/10, v/v, over 12 min), to give the title compound (60 mg, 81%). LC/MS: m/z, 531 (M+H), 2.83 min.

Workup

  1. customThe resulting solution was irradiated in a microwave reactor at 150° C. for 20 minutes
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was further extracted by EtOAc (2×5 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by Gilson HPLC
  8. washeluting with acetonitrile/water/0.1% TFA (10/90 to 90/10

Sources & evidence

ORD record
ord-241fc089774740ae9658edfced4b3ec6
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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