Diisopropylethylamine → Propylene Glycol Dioleate

HRID 1055179Notes

Reaction equation

HRID 1055179 reaction equation
N(C(OC(C)(C)C)=O)CC(NCC(NCC(O)=O)=O)=O.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[C:54]([O:73][CH2:74][C@H:75]([CH2:96]OP(OCCN)(O)=O)[O:76][C:77](=[O:95])[CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84]/[CH:85]=[CH:86]\[CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH2:92][CH2:93][CH3:94])(=[O:72])[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61]/[CH:62]=[CH:63]\[CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH3:71].Cl.C(OCC)C>CN(C=O)C.C(Cl)(Cl)Cl>[C:54]([O:73][CH2:74][CH:75]([O:76][C:77](=[O:95])[CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84]/[CH:85]=[CH:86]\[CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH2:92][CH2:93][CH3:94])[CH3:96])(=[O:72])[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61]/[CH:62]=[CH:63]\[CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH3:71]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 7019030Boc-gly-gly-gly-OHHCID 95467571,2-Dioleoyl-sn-glycero-3-phosphoethanolamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10953452Ether hydrochloride

Product 1

HCID 6436863Propylene Glycol DioleateYield 112.9%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

Boc-Gly-Gly-Gly-OH (382 mg, 1.34 mmol) and N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (532 mg, 1.4 mmol) were dissolved in DMF (5 mL). N,N-Diisopropylethylamine (488 uL, 2.8 mmol) was added and the mixture was allowed to stir at room temperature for 10-15 minutes. Afterwards, a solution of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (833 mg, 1.12 mmol) in chloroform (5 mL) was added and the reaction vessel was flushed with argon. After 16 hours at room temperature, the reaction mixture was concentrated and partitioned between dichloromethane (50 mL) and H2O (50 mL), extracted with dichloromethane (3×50 mL), dried with sodium sulfate, filtered and concentrated. Material was purified via silica gel chromatography using a dichloromethane/methanol gradient to yield colorless oil residue. To this, 2 M HCl/Diethyl Ether (5 mL) was added and the reaction mixture was allowed to stir in a H2O bath for approximately 2 hours. The reaction mixture was concentrated and the residue was taken up in dichloromethane (75 mL), washed with saturated sodium bicarbonate solution (75 mL), extracted product with dichloromethane (3×75 mL), dried with sodium sulfate, filtered and concentrated to yield (Z)-(2R)-3-(2-(2-(2-(2-aminoacetamido)acetamido)acetamido)ethoxy)(hydroxy)phosphoryl)oxy)propane-1,2-diyl dioleate as a semi-solid (765 mg, 90%). Verified by NMR.

Workup

  1. customthe reaction vessel was flushed with argon
  2. waitAfter 16 hours at room temperature
  3. concentrationthe reaction mixture was concentrated
  4. custompartitioned between dichloromethane (50 mL) and H2O (50 mL)
  5. extractionextracted with dichloromethane (3×50 mL)
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customMaterial was purified via silica gel chromatography
  10. customto yield colorless oil residue
  11. stirringto stir in a H2O bath for approximately 2 hours
  12. concentrationThe reaction mixture was concentrated
  13. washwashed with saturated sodium bicarbonate solution (75 mL)
  14. extractionextracted product with dichloromethane (3×75 mL)
  15. dry with materialdried with sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-49f817caad8341e198295d5c34c70d5a
Source dataset
uspto-grants-2016_07
Patent number
US09393315B2

Reaction notes

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