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Triethylamine → 1-Benzyl-3-[((9Z,12Z)-Octadeca-9,12-Dienyl)Oxy]-4-Octyloxy-Pyrrolidine

HRID 2176953
Notes
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Reaction equation

HRID 2176953 reaction equation
C1(S(O)(=O)=O)C=CC=CC=1.[CH2:11]([N:18]1[CH2:22][CH:21]([OH:23])[CH:20]([OH:24])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.[H-].[Na+].S(O[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])(=O)(=O)C.C([O-])([O-])=O.[K+].[K+].S(O[C:58](=O)[CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65]/[CH:66]=[CH:67]\[CH2:68]/[CH:69]=[CH:70]\[CH2:71][CH2:72][CH2:73][CH2:74][CH3:75])(=O)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[CH2:11]([N:18]1[CH2:22][CH:21]([O:23][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[CH:20]([O:24][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65]/[CH:66]=[CH:67]\[CH2:68]/[CH:69]=[CH:70]\[CH2:71][CH2:72][CH2:73][CH2:74][CH3:75])[CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 6

HCID 8471Triethylamine2×HCID 11430Potassium CarbonateHCID 24758Sodium hydride2×HCID 11790439Octyl methanesulfonateHCID 86694888Linoleoyl mesylateHCID 1317329961-Benzyl-3,4 dihydroxy pyrroldine benzene sulfonic acid salt

Product 1

HCID 675138381-Benzyl-3-[((9Z,12Z)-Octadeca-9,12-Dienyl)Oxy]-4-Octyloxy-PyrrolidineYield 62.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
50 °C

Procedure

In 500 mL 3N RBF, compound 1 (18 g, 51.2 mmol) and triethylamine (0.714 ml, 5.12 mmol) were suspended in 180 mL toluene for addition of the sodium hydride (4.30 g, 108 mmol). Heated suspension to 50° C. for 1 h. Cooled back to 23° C. and then added the n-octyl mesylate (10.67 g, 51.2 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 7.22 g of a slightly yellow oil. In 500 mL 3N RBF, 4.04 g of the aforementioned oil (13.23 mmol) and triethylamine (0.184 ml, 1.323 mmol) was dissolved in 80 mL toluene for addition of the sodium hydride (0.582 g, 14.55 mmol). Heated suspension to 50° C. for 1 h. Cooled back to 23° C. and then added the linoleoyl mesylate (5.01 g, 14.55 mmol). Heated slurry up to 80° C. for 21 h or until complete disappearance 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 5.02 g of 2 as a clear oil (33% yield over 2 steps). 1H NMR (400 MHz, CDCl3) δ7.28 (m, 5H), 5.40 (m, 4H), 3.85 (Ψt, J=4.8 Hz, 2H), 3.61 (m, 2H), 3.42 (m, 4H), 2.88 (dd, J=9.7, 6.1 Hz, 2H), 2.79 (Ψt, J=6.4 Hz, 2H). 2.51 (dd, J=10.1, 4.2 Hz, 21-1), 2.06 (q, J=6.7 Hz, 2H), 1.56 (q, 4H), 1.41-1.29 (m, 26H), 0.9 (m, 6H).

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 7.22 g of 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-b1abdd26e81847f99878d70d00ff1bf8
Source dataset
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09067882B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes