Hydrochloric Acid → tert-butyl 4-[2-(3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)ethyl]piperazine-1-carboxylate

HRID 1519499Notes

Reaction equation

HRID 1519499 reaction equation
Cl.O1CCO[CH:3]1[CH2:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[C:14](=[O:18])[O:13][CH:12]([CH3:19])[CH2:11]2.[C:20]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCOCC1>[CH3:19][CH:12]1[CH2:11][C:10]2[C:15](=[CH:16][CH:17]=[C:8]([CH2:7][CH2:3][N:30]3[CH2:29][CH2:28][N:27]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:32][CH2:31]3)[CH:9]=2)[C:14](=[O:18])[O:13]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 675173636-(1,3-dioxolan-2-ylmethyl)-3-methyl-3,4-dihydro-1H-isochromen-1-one

Product 1

HCID 67516023tert-butyl 4-[2-(3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)ethyl]piperazine-1-carboxylateYield 70.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A 1:1 solution of dioxane:3N HCl was added to a flask containing of 780 mg (3.2 mmol) of 6-(1,3-dioxolan-2-ylmethyl)-3-methyl-3,4-dihydro-1H-isochromen-1-one. The reaction was then stirred at room temp overnight. The crude reaction mixture was then partitioned between water and DCM. The organic layer was washed with saturated sodium bicarbonate solution, followed by brine. The organic layer was then dried with magnesium sulfate, filtered and concentrated. The crude aldehyde was redissolved in DCM. To the solution was added boc-piperazine (671 mg, 3.6 mmol) followed by sodium triacetoxyborohydride (1.9 g, 9.0 mmol). the reaction mixture was allowed to stir overnight before being quenched with 10 mL of MeOH. The excess solvent was removed and the residue was re-redissolved in DCM; washed with water and brine, dried with magnesium sulfate, filtered, concentrated and purified via MPLC (50-100% EtOAc/Hex) to afford 850 mg of tert-butyl 4-[2-(3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl)ethyl]piperazine-1-carboxylate as a golden oil. 1H NMR (500 MHz; CDCl3): 8.02 (d, J=7.8 Hz, 1H), 7.24 (d, J=7.7 Hz, 1H), 7.09 (s, 1H), 4.68 (m, 1H), 3.49 (m, 4H), 2.94 (m, 4H), 2.88 (m, 2H), 2.51 (m, 4H), 1.54 (d, J=6.8 Hz, 3H), 1.48 (s, 9H). LC-MS (IE, m/z): 375 [M+1]+.

Workup

  1. customThe crude reaction mixture
  2. customwas then partitioned between water and DCM
  3. washThe organic layer was washed with saturated sodium bicarbonate solution
  4. dry with materialThe organic layer was then dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude aldehyde was redissolved in DCM
  8. stirringto stir overnight
  9. custombefore being quenched with 10 mL of MeOH
  10. customThe excess solvent was removed
  11. dissolutionthe residue was re-redissolved in DCM
  12. washwashed with water and brine
  13. dry with materialdried with magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. custompurified via MPLC (50-100% EtOAc/Hex)

Sources & evidence

ORD record
ord-de0219e93d3f4e5d98e15f015ac5a6bd
Source dataset
uspto-grants-2015_07
Patent number
US09073882B2

Reaction notes

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