Triethylamine → Benzyl 3-[(9Z,12Z)-Octadeca-9,12-Dien-1-Yloxy]-4-(Octyloxy)Pyrrolidine-1-Carboxylate

HRID 2176955Notes

Reaction equation

HRID 2176955 reaction equation
[OH:1][CH:2]1[CH:6]([OH:7])[CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:3]1.C(N(CC)CC)C.[H-].[Na+].S(O[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]/[CH:40]=[CH:41]\[CH2:42]/[CH:43]=[CH:44]\[CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])(=O)(=O)C.C([O-])([O-])=O.[K+].[K+].S(O[CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH3:68])(=O)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[CH2:32]([O:1][CH:2]1[CH:6]([O:7][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH3:68])[CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:3]1)[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]/[CH:40]=[CH:41]\[CH2:42]/[CH:43]=[CH:44]\[CH2:45][CH2:46][CH2:47][CH2:48][CH3:49]

Participants

9

Reactant 6

HCID 8471Triethylamine2×HCID 11430Potassium CarbonateHCID 24758Sodium hydride2×HCID 11790439Octyl methanesulfonateHCID 14771964Benzyl 3,4-dihydroxypyrrolidine-1-carboxylateHCID 59753235Linoleyl methanesulfonate

Product 1

HCID 86694890Benzyl 3-[(9Z,12Z)-Octadeca-9,12-Dien-1-Yloxy]-4-(Octyloxy)Pyrrolidine-1-CarboxylateYield 77.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
50 °C

Procedure

In 2500 mL RBF, compound 9 (9.7 g, 40.0 mmol) and triethylamine (0.558 ml, 4.0 mmol) were suspended in 100 mL toluene for addition of the sodium hydride (1.76 g, 44 mmol). Heated suspension to 50° C. for 1 h. Cooled back to 23° C. and then added the linoleyl mesylate (13.8 g, 40.0 mmol). Heated slurry up to 80° C. for 18 h. Cooled to 23° C. and poured into 200 mL 1M K2CO3. Extracted with methyl tert-butyl ether (MTBE) and then dried combiend layers over Na2SO4. Filtered, concentrated and purified oil by silica gel chromatogtaphy to obtain monoalkylated product as a slightly yellow oil. In 250 mL RBF, 8 g of the aforementioned oil (16.47 mmol) and triethylamine (0.23 ml, 1.65 mmol) was dissolved in 100 mL toluene for addition of the sodium hydride (0.0.725 g, 18.12 mmol). Heated suspension to 50° C. for 1 h. Cooled back to 23° C. and then added the n-octyl mesylate (3.77 g, 18.12 mmol). Heated slurry up to 80° C. for 21 h or until complete dissappearance of the starting material was observed by HPLC. Cooled to 23° C., diluted with 100 mL hexane and washed with 100 mL 1M K2CO3. Extracted aquoues layer with 100 mL hexane and then washed combined organic layers with 100 mL brine and dried over MgSO4. Filtered and concentrated. Purified by silica gel chromatography to obtain 8.4 g of 10 as a clear oil. Product contains some octyl mesylate but was carried into next reaction.

Workup

  1. temperatureCooled back to 23° C.
  2. temperatureHeated slurry up to 80° C. for 18 h
  3. temperatureCooled to 23° C.
  4. extractionExtracted with methyl tert-butyl ether (MTBE)
  5. dry with materialdried combiend layers over Na2SO4
  6. filtrationFiltered
  7. concentrationconcentrated
  8. custompurified oil by silica gel chromatogtaphy
  9. customto obtain monoalkylated product as a slightly yellow oil
  10. temperatureHeated suspension to 50° C. for 1 h
  11. temperatureCooled back to 23° C.
  12. temperatureHeated slurry up to 80° C. for 21 h
  13. temperatureCooled to 23° C.
  14. washwashed with 100 mL 1M K2CO3
  15. washExtracted aquoues layer with 100 mL hexane and then washed
  16. dry with materialdried over MgSO4
  17. filtrationFiltered
  18. concentrationconcentrated
  19. customPurified by silica gel chromatography

Sources & evidence

ORD record
ord-8b5f276fcb9c40c8a8b3cfd049326e79
Source dataset
uspto-grants-2015_06
Patent number
US09067882B2

Reaction notes

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