Potassium Carbonate → 1,1-Dimethylethyl (2S)-4-{[3-(4-cyano-2-pyridinyl)phenyl]methyl}-2-methyl-1-piperazinecarboxylate

HRID 564575Notes

Reaction equation

HRID 564575 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.[CH3:10][C@H:11]1[CH2:16][N:15]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20](B3OC(C)(C)C(C)(C)O3)[CH:19]=2)[CH2:14][CH2:13][N:12]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:22]2[CH:23]=[C:18]([CH2:17][N:15]3[CH2:14][CH2:13][N:12]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@@H:11]([CH3:10])[CH2:16]3)[CH:19]=[CH:20][CH:21]=2)[CH:7]=1)#[N:9]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 5686382-Chloro-4-cyanopyridineHCID 578132571,1-dimethylethyl (2S)-2-methyl-4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperazinecarboxylate

Product 1

HCID 578134861,1-Dimethylethyl (2S)-4-{[3-(4-cyano-2-pyridinyl)phenyl]methyl}-2-methyl-1-piperazinecarboxylateYield 94%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To 2-chloro-4-pyridinecarbonitrile (0.416 g, 3 mmol) was added 1,1-dimethylethyl (2S)-2-methyl-4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperazinecarboxylate (1.499 g, 3.60 mmol) followed by K2CO3 (1.244 g, 9.00 mmol) and Pd(Ph3P)4 (0.139 g, 0.120 mmol) in 1,4-dioxane (15.00 mL) and water (5.00 mL). The mixture was heated in a microwave oven for 30 min at 140° C. The organic layer was collected and the aqueous layer was extracted once with EtOAc (3 mL). The combined organic layers were filtered, concentrated on Glas-Col, redissolved in hexane/DCM (3:1, 4 mL), loaded onto Redisep silica gel column (12 g) and purified with Combiflash chromatography. Fractions were collected and the solvent was removed under reduced pressure to afford 1.10 g (94%) of the title compound. LC-MS m/z 393 (M+H)+.

Workup

  1. customThe organic layer was collected
  2. extractionthe aqueous layer was extracted once with EtOAc (3 mL)
  3. filtrationThe combined organic layers were filtered
  4. concentrationconcentrated on Glas-Col
  5. dissolutionredissolved in hexane/DCM (3:1, 4 mL)
  6. custompurified with Combiflash chromatography
  7. customFractions were collected
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-dd347c4322ad4c22bdffd41126c65be1
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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