Dimethylformamide → HCID 178451155, compound

HRID 2272644Notes

Reaction equation

HRID 2272644 reaction equation
[CH2:1]([O:5][C:6]([C@H:8]1[CH2:13][CH2:12][C@H:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].[CH3:17]N(C=O)C.C(Cl)(=O)C(Cl)=O.C[Zn]C>C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:14]([C@H:11]1[CH2:10][CH2:9][C@H:8]([C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])=[O:7])[CH2:13][CH2:12]1)(=[O:16])[CH3:17]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 178451162HCID 178451162, compoundHCID 178477796HCID 178477796, compound

Product 1

HCID 178451155HCID 178451155, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a vented and cooled solution (0° C.) under nitrogen of trans-4-(butoxycarbonyl)cyclohexanecarboxylic acid (J. Chem. Soc., Perkin Trans. 1, 1999, 20, 3023) (18.9 g, 83 mmol) in CH2Cl2 (150 mL) was added a catalytic amount of DMF (30 μL) followed by oxalyl chloride (7.97 mL, 91 mmol). The reaction mixture was then allowed to slowly warm to room temperature where it was stirred for 14 h at which point it was concentrated to a yellow oil and dried under vacuum for 3 h. The residue consisting primarily of butyl trans-4-(chlorocarbonyl)cyclohexanecarboxylate was diluted with THF (200 mL) and cooled in an ice bath. To this solution was added PdCl2(dppf)-CH2Cl2 (3.38 g, 4.14 mmol) followed by dimethyl zinc (2 M in PhCH3, 29 mL, 58 mmol) at such a rate that the internal temperature did not exceed 15° C. The cooling bath was then removed and after 2 h of stirring at room temperature the reaction mixture was re-cooled to 0° C. where it was diluted carefully with H2O. After the initial exotherm had subsided, sufficient 1N HCl and EtOAc were introduced such that a homogenous biphasic mixture formed. The layers were separated, the organic washed a second time with H2O then dried with MgSO4, filtered and concentrated in vacuo. The crude residue was absorbed on silica and purified by flash chromatography to afford butyl trans-4-acetylcyclohexanecarboxylate as a non-viscous orange oil. MS ESI calc'd. for C13H23O3 [M+H]+ 227. found 227. 1H NMR (500 MHz, CDCl3) δ 4.06 (t, J=6.6 Hz, 2H), 2.37-2.29 (m, 1H), 2.28-2.20 (m, 1H), 2.14 (s, 3H), 2.11-2.02 (m, 2H), 1.99 (d, J=13.8 Hz, 2H), 1.66-1.55 (m, 2H), 1.51-1.40 (m, 2H), 1.39-1.29 (m, 4H), 0.93 (t, J=7.4 Hz, 3H).

Workup

  1. concentrationwas concentrated to a yellow oil
  2. customdried under vacuum for 3 h
  3. additionwas diluted with THF (200 mL)
  4. temperaturecooled in an ice bath
  5. customdid not exceed 15° C
  6. customThe cooling bath was then removed and after 2 h
  7. stirringof stirring at room temperature the reaction mixture
  8. temperaturewas re-cooled to 0° C. where it
  9. additionwas diluted carefully with H2O
  10. additionsufficient 1N HCl and EtOAc were introduced such that a homogenous biphasic mixture
  11. customformed
  12. customThe layers were separated
  13. washthe organic washed a second time with H2O
  14. dry with materialthen dried with MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customThe crude residue was absorbed on silica
  18. custompurified by flash chromatography

Sources & evidence

ORD record
ord-f4ee85c7b0e646649cf7b216929c0e3b
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

Loading…