Benzoyl chloride → HCID 131732043, compound

HRID 337695Notes

Reaction equation

HRID 337695 reaction equation
C([Cu])#N.[Li+].[Cl-].[Br:6][C:7]1[CH:8]=[C:9]([CH:38]=[C:39](I)[CH:40]=1)[CH2:10][N:11]([CH:35]1[CH2:37][CH2:36]1)[C:12]([C@H:14]1[C@H:19]([C:20]2[CH:25]=[CH:24][N:23]([CH3:26])[C:22](=[O:27])[CH:21]=2)[CH2:18][CH2:17][N:16]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:15]1)=[O:13].[C:42](Cl)(=[O:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C1COCC1>[C:42]([C:39]1[CH:38]=[C:9]([CH:8]=[C:7]([Br:6])[CH:40]=1)[CH2:10][N:11]([CH:35]1[CH2:37][CH2:36]1)[C:12]([C@H:14]1[C@H:19]([C:20]2[CH:25]=[CH:24][N:23]([CH3:26])[C:22](=[O:27])[CH:21]=2)[CH2:18][CH2:17][N:16]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:15]1)=[O:13])(=[O:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 7412Benzoyl chlorideHCID 433294Lithium ChlorideHCID 131732044HCID 131732044, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 131732043HCID 131732043, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1,5-bis(bromomagnesium)pentane (1.0 eq.) in THF (0.05 M) at −78° C. was added a solution of CuCN-2LiCl prepared from CuCN (1.0 eq.) and LiCl (2.0 eq.) in THF (0.9 M with respect to CuCN). The resulting mixture was stirred at −78° C. for 30 min. A solution of trans-tert-butyl 3-{[(3-bromo-5-iodobenzyl)(cyclopropyl)amino]carbonyl}-4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-1-piperidinecarboxylate (1.0 eq.) from the previous step in THF (0.2 M) was then added and the reaction mixture was warmed to RT over 1 h. Finally, benzoyl chloride (1.5 eq.) was added and the reaction mixture was stirred for another hour. The reaction mixture was quenched with the addition of water and subsequently extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 2:98 (v/v)→15:85 (v/v) MeOH:CH2Cl2) afforded the title compound as a brown oil.

Workup

  1. temperaturethe reaction mixture was warmed to RT over 1 h
  2. stirringthe reaction mixture was stirred for another hour
  3. customThe reaction mixture was quenched with the addition of water
  4. extractionsubsequently extracted with EtOAc
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated in vacuo
  8. customPurification of the crude product
  9. customthus obtained by way of flash chromatography (SiO2, 2:98 (v/v)→15:85 (v/v) MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-b75e797c18d94c94a837958f9acd50fb
Source dataset
uspto-grants-2014_11
Patent number
US08889714B2

Reaction notes

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