Acetone cardice → HCID 66833120, compound

HRID 579602Notes

Reaction equation

HRID 579602 reaction equation
CON(C)[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:8][CH2:7]1)=[O:5].C(=O)=O.CC(C)=O.[CH2:30]([Mg]Br)[CH2:31][CH:32]=[CH2:33]>C1COCC1>[C:4]([CH:6]1[CH2:7][CH2:8][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[CH2:10][CH2:11]1)(=[O:5])[CH2:33][CH2:32][CH:31]=[CH2:30]

Participants

5

Reactant 3

HCID 18522661Acetone cardiceHCID 22574154Benzyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateHCID 178418797HCID 178418797, compound

Product 1

HCID 66833120HCID 66833120, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

While under an argon atmosphere, a solution of benzyl 4-(methoxy(methyl) carbamoyl)piperidine-1-carboxylate (15.0 g, 49.0 mmol) in THF (100 mL) was cooled to −78° C. (dry ice/acetone bath) and treated with 3-butenylmagnesium bromide (250 mL, 0.5 M sol. in THF, 125 mmol, Aldrich) via canula. After the addition was complete, the cooling bath was removed allowing the solution to slowly warm to room temperature. After stirring overnight (16 h), the reaction mixture was quenched with 0.1N HCl (200 mL) and diluted with ethyl acetate (300 mL). After stirring an additional 5 min, the organic phase was separated, washed with saturated sodium bicarbonate (200 mL), dried over MgSO4, filtered and concentrated. Purification by MPLC (100 g column, 20-50% ethyl acetate in heptane) gave benzyl 4-pent-4-enoylpiperidine-1-carboxylate (14.5, 98%) as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 7.38-7.32 (m, 5H), 5.79 (dddd, J1=17.1 Hz, J2=10.2 Hz, J3=6.9 Hz, J4=6.6 Hz, 1H), 5.12 (s, 2H), 5.02 (dd, J1=17.1 Hz, J2=1.5 Hz, 1H), 4.97 (dd, J1=10.2 Hz, J2=1.5 Hz, 1H), 4.28-4.10 (m, 2H), 2.86 (br t, J=12 Hz, 2H), 2.58-2.43 (m, 3H), 2.35-2.28 (m, 2H), 1.9-1.74 (m, 2H), 1.62-1.48 (m, 2H). ESI MS found for C18H23NO3 m/z [302.3 (M+1), 324.1 (M+23)].

Workup

  1. additionAfter the addition
  2. customthe cooling bath was removed
  3. customthe reaction mixture was quenched with 0.1N HCl (200 mL)
  4. additiondiluted with ethyl acetate (300 mL)
  5. stirringAfter stirring an additional 5 min
  6. customthe organic phase was separated
  7. washwashed with saturated sodium bicarbonate (200 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by MPLC (100 g column, 20-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-9a741d0e85f846899381134b1f978c52
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

Loading…