Sodium Carbonate → 1,1-Dimethylethyl (2S)-4-[(3'-cyano-4'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 2080309Notes

Reaction equation

HRID 2080309 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].Br[C:14]1[CH:15]=[C:16]([CH2:20][N:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@@H:23]([CH3:34])[CH2:22]2)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[C:1]([C:3]1[CH:4]=[C:5]([C:18]2[CH:19]=[CH:14][CH:15]=[C:16]([CH2:20][N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@@H:23]([CH3:34])[CH2:22]3)[CH:17]=2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27579643-Cyano-4-fluorophenylboronic acidHCID 577367121,1-dimethylethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylate

Product 1

HCID 577367021,1-Dimethylethyl (2S)-4-[(3'-cyano-4'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylateYield 73.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3-cyano-4-fluorophenyl)boronic acid (0.983 g, 5.96 mmol) in DME (40 mL) was added 1,1-dimethylethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylate (2.20 g, 5.96 mmol) followed by Na2CO3 (17 mL, 2M in H2O, 34.0 mmol). The reaction vessel was flushed with Ar, and tetrakis(triphenylphosphine)palladium(0) (2.06 g, 1.78 mmol) was added. The reaction mixture was placed in an oil bath at 78° C. under Ar for overnight. The reaction was diluted with EtOAc (600 mL) and washed with H2O (250 mL). The water layer was extracted with EtOAc (1×100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. Purification of the crude residue by flash chromatography (20% EtOAc/80% hexane) on silica gel gave the title compound (1.77 g, 73.1%). EI-MS m/z 410 (M−H)+.

Workup

  1. additionwas added
  2. washwashed with H2O (250 mL)
  3. extractionThe water layer was extracted with EtOAc (1×100 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customPurification of the crude residue by flash chromatography (20% EtOAc/80% hexane) on silica gel

Sources & evidence

ORD record
ord-c2a2bdf4987246c1b8a858c909f275ab
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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