Stannanecarbonitrile, tributyl- → 3-{(R*)-1-[(S)-1-(2,3-Dihydrobenzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl}-benzonitrile

HRID 453759Notes

Reaction equation

HRID 453759 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[CH2:11][N:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([C:18]2[CH:19]=[C:20](OS(C(F)(F)F)(=O)=O)[CH:21]=[CH:22][CH:23]=2)[CH2:13]1.C([Sn]([C:45]#[N:46])(CCCC)CCCC)CCC>ClCCCl.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>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[CH2:11][N:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([C:18]2[CH:19]=[C:20]([CH:21]=[CH:22][CH:23]=2)[C:45]#[N:46])[CH2:13]1

Participants

5

Reactant 2

HCID 200512Stannanecarbonitrile, tributyl-HCID 86644712Trifluoromethanesulfonic acid 3-{(R*)-1-[(S)-1-(2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl}phenyl ester

Product 1

HCID 251751673-{(R*)-1-[(S)-1-(2,3-Dihydrobenzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl}-benzonitrileYield 7.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of trifluoromethanesulfonic acid 3-{(R*)-1-[(S)-1-(2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]-piperidin-3-yl}phenyl ester (51 mg, 0.11 mmol), tributyltin cyanide (142 mg, 0.45 mmol) and tetrakis(triphenylphosphine)palladium (189 mg, 0.164 mmol) in 1,2-dichloroethane (15 ml) was heated in a microwave reactor at 80° C. for 80 h. The solid precipitate was filtered off and the mixture was evaporated to dryness. The residue was redissolved in DCM, filtered and washed two times with 1 M HCl. The combined organic phases were washed with brine, dried (Na2SO4) and evaporated to dryness. The crude product was purified by flash chromatography first using gradient of DCM and MeOH and then using gradient of heptane and EtOAc as eluent to give 2.8 mg of the title compound.

Workup

  1. filtrationThe solid precipitate was filtered off
  2. customthe mixture was evaporated to dryness
  3. dissolutionThe residue was redissolved in DCM
  4. filtrationfiltered
  5. washwashed two times with 1 M HCl
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated to dryness
  9. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-5430ceb4d5e64115a9b8ced0dad0f8b5
Source dataset
uspto-grants-2013_07
Patent number
US08492549B2

Reaction notes

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