2-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride) → 4-(2-Trifluoromethoxy-benzoyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 713422Notes

Reaction equation

HRID 713422 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1B(O)O.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([C:28](SC2C=CC=CC=2C)=[O:29])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].S1C=CC=C1C([O-])=O.[Cu+]>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([C:28](=[O:29])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[O:3][C:2]([F:14])([F:13])[F:1])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 2

HCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 117819078p-Tolylsulfanylcarbonyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 1178188874-(2-Trifluoromethoxy-benzoyl)-piperidine-1-carboxylic acid tert-butyl esterYield 89.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of 2-trifluoromethoxy-phenyl-boronic acid (0.307 g, 2.24 mmol, 1.5 eq.), ligand TFP (0.069 g, 0.298 mmol, 0.2 eq.), Pd2(dba)3 (0.154 g, 0.149 mmol, 0.1 eq.), copper (I) thiophene-2-carboxylate (0.426 g, 2.24 mmol, 1.5 eq.) was added a solution of p-tolylsulfanylcarbonyl-piperidine-1-carboxylic acid tert-butyl ester (0.479 g, 1.49 mmol, 1 eq.) in 15 mL of DME while purging with N2 at room temperature. After 18 h stirring at room temperature, the reaction mixture was diluted with ethyl acetate and filtered through celite. The filtrate was concentrated to give an oil. This oil was purified by silica gel column chromatography (10% ethyl acetate/heptane) to give the title compound as a white solid (0.5 g, 86%). Exact mass calculated for C18H23F3N1O4 374.2. MS (ESI) m/z 274.3 [(M-100)H]+.

Workup

  1. customwhile purging with N2 at room temperature
  2. additionthe reaction mixture was diluted with ethyl acetate
  3. filtrationfiltered through celite
  4. concentrationThe filtrate was concentrated
  5. customto give an oil
  6. customThis oil was purified by silica gel column chromatography (10% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-8d99f16068cc49e6b42a7d85fc6fd027
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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