Methanol → tert-butyl 4-[2-(5-hydroxy-7-oxo-5H-[1,3]dioxolo[4,5-f]isoindol-6-yl)ethyl]piperidine-1-carboxylate

HRID 528503Notes

Reaction equation

HRID 528503 reaction equation
[O:1]=[C:2]1[C:10]2[CH:9]=[C:8]3[O:11][CH2:12][O:13][C:7]3=[CH:6][C:5]=2[C:4](=[O:14])[N:3]1[CH2:15][CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.CO.O1CCCC1.[BH4-].[Na+]>O>[OH:14][CH:4]1[C:5]2[CH:6]=[C:7]3[O:13][CH2:12][O:11][C:8]3=[CH:9][C:10]=2[C:2](=[O:1])[N:3]1[CH2:15][CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 90064408Tert-butyl 4-[2-(5,7-dioxo-[1,3]dioxolo[4,5-f]isoindol-6-yl) ethyl]piperidine-1-carboxylate

Product 1

HCID 90064479tert-butyl 4-[2-(5-hydroxy-7-oxo-5H-[1,3]dioxolo[4,5-f]isoindol-6-yl)ethyl]piperidine-1-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a reaction vessel, 92 g (0.23 mol) compound XI, 250 ml methanol and 250 ml tetrahydrofuran were added while stirring, the mixture was cooled to 0˜10° C., 10 g (0.26 mol) sodium borohydride was added, the reaction was kept at 0˜10° C. for 20-30 min, 100 ml water was added, the reaction mixture was concentrated to dry under reduced pressure (at 45° C.), The residue was added 500 ml ethyl acetate and 300 ml water, and extracted, the organic layer was collected, dried over sodium sulfate, concentrated to a minor amount, 300 ml petroleum ether was added, a solid was precipitated out, filtered, the filter cake was washed wth petroleum ether, dried, and 64.7 g compound VII-1 was obtained, with yield of 70%. 1H NMR (DMSO-d6): δ 0.95-1.04 (m, 2H), 1.39 (s, 10H), 1.51 (m, 2H), 1.70 (dd, 2H, J=25.0, 12.4 Hz), 2.65 (br s, 2H), 3.23-3.30 (m, 1H), 3.54-3.61 (m, 1H), 3.90 (d, 2H, J=10.0 Hz), 5.67 (d, 1H, J=8.9 Hz), 6.12 (s, 1H), 6.13 (s, 1H), 6.50 (d, 1H, J=9.0 Hz), 7.08 (s, 1H), 7.09 (s, 1H); MS (ESI): m/z 427 [M+Na]+.

Workup

  1. temperaturethe mixture was cooled to 0˜10° C.
  2. concentrationthe reaction mixture was concentrated
  3. customto dry under reduced pressure (at 45° C.)
  4. additionThe residue was added 500 ml ethyl acetate and 300 ml water
  5. extractionextracted
  6. customthe organic layer was collected
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to a minor amount, 300 ml petroleum ether
  9. additionwas added
  10. customa solid was precipitated out
  11. filtrationfiltered
  12. washthe filter cake was washed wth petroleum ether
  13. customdried

Sources & evidence

ORD record
ord-4f4f03fd14db462c868fbd12c798df63
Source dataset
uspto-grants-2016_05
Patent number
US09346818B2

Reaction notes

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