Hydrochloric Acid → HCID 86592521, compound

HRID 1374412Notes

Reaction equation

HRID 1374412 reaction equation
[OH:1][CH:2]1[CH2:7][N:6]([C:8]([O:10][CH2:11][CH:12]=[CH2:13])=[O:9])[C@@H:5]([CH2:14][O:15][CH2:16][O:17][CH3:18])[CH2:4][CH:3]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].[CH3:26][S:27](Cl)(=[O:29])=[O:28].C(N(CC)CC)C.Cl.C1CCN2C(=NCCC2)CC1>ClCCl.CN(C)C1C=CN=CC=1>[CH3:18][O:17][CH2:16][O:15][CH2:14][C@H:5]1[CH2:4][CH:3]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:2]([O:1][S:27]([CH3:26])(=[O:29])=[O:28])[CH2:7][N:6]1[C:8]([O:10][CH2:11][CH:12]=[CH2:13])=[O:9].[CH3:18][O:17][CH2:16][O:15][CH2:14][C@H:5]1[CH2:4][C:3]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:2][CH2:7][N:6]1[C:8]([O:10][CH2:11][CH:12]=[CH2:13])=[O:9]

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86592519HCID 86592519, compound

Product 2

HCID 86592520HCID 86592520, compoundYield 15%HCID 86592521HCID 86592521, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-allyl 4-tert-butyl (2R)-5-hydroxy-2-[(methoxymethoxy)methyl]-1,4-piperidinedicarboxylate (1.22 g, 3.4 mmol) in dichloromethane (9.4 ml) were added at −30° C. methanesulfonyl chloride (0.4 ml, 5.1 mmol), triethylamine (0.95 ml, 6.8 mmol) and 4-dimethylaminopyridine ((41.5 mg, 0.34 mmol), and the mixture was stirred 0° C. for 40 minutes. The reaction mixture was poured into diluted hydrochloric acid and the mixture was extracted three times with chloroform. The organic layer was washed with a saturated aqueous sodium chloride, and dried over magnesium sulfate. The organic solvent was removed under reduced pressure, and the residue was dissolved in toluene (5 ml) and dichloromethane (10 ml). The mixture was cooled to 0° C. and thereto was added DBU (0.76 ml, 5.1 mmol). The mixture was raised to room temperature and was stirred accurately for 20 minutes. The reaction mixture was poured into diluted hydrochloric acid and extracted three times with ethyl acetate. The organic layer was washed with water and then a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate and the organic solvent was removed under reduced pressure. The residue was purified by silica gel (30 g) chromatography (Hexane/ethyl acetate: 2/1) to give 1-allyl 4-tert-butyl (2R)-2-[(methoxymethoxy)methyl]-5-[(methylsulfonyl)oxy]-1,4-piperidinedicarboxylate (0.24 g, 15%) and 1-allyl 4-tert-butyl (2R)-2-[(methoxymethoxy)methyl]-3,6-dihydro-1,4(2 H)-pyridinedicarboxylate (0.79 g, 68%).

Workup

  1. extractionthe mixture was extracted three times with chloroform
  2. washThe organic layer was washed with a saturated aqueous sodium chloride
  3. dry with materialdried over magnesium sulfate
  4. customThe organic solvent was removed under reduced pressure
  5. dissolutionthe residue was dissolved in toluene (5 ml)
  6. temperatureThe mixture was cooled to 0° C.
  7. temperatureThe mixture was raised to room temperature
  8. stirringwas stirred accurately for 20 minutes
  9. extractionextracted three times with ethyl acetate
  10. washThe organic layer was washed with water
  11. dry with materialThe organic layer was dried over magnesium sulfate
  12. customthe organic solvent was removed under reduced pressure
  13. customThe residue was purified by silica gel (30 g) chromatography (Hexane/ethyl acetate: 2/1)

Sources & evidence

ORD record
ord-cabd0f84b1ed46779ffe7440e4f97456
Source dataset
uspto-grants-2007_01
Patent number
US07163936B2

Reaction notes

Loading…