Acetic Acid → N-methyl-N-(t-Boc)-PEG4-acid

HRID 446654Notes

Reaction equation

HRID 446654 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:9])([CH3:6])([CH3:5])[CH3:4].IC.[C:30](O)(=O)C>C1COCC1>[C:3]([O:7][C:8]([N:10]([CH3:30])[CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6328Methyl iodide3×HCID 24758Sodium hydride2×HCID 27560011-(((Tert-butoxy)carbonyl)amino)-3,6,9,12-tetraoxapentadecan-15-oic acid

Product 1

HCID 86671296N-methyl-N-(t-Boc)-PEG4-acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

85.4 mg of NaH are added portionwise to a solution, cooled to 0° C., of 520 mg of 3-[2-(2-{2-[2-((tert-butoxycarbonyl)amino)ethoxy]ethoxy}ethoxy)ethoxy]propanoic acid in 14 ml of THF. After stirring for 5 min, 150 μl of iodomethane are added. The mixture is then stirred at AT for 2 h and then an additional 150 μl of iodomethane are added. After 12 h at AT, the mixture is hydrolysed and then brought to acidic pH by addition of aqueous acetic acid at 0° C. The aqueous phase is extracted 3× with AcOEt, the combined organic phases are dried over MgSO4 and concentrated under RP, and the crude product obtained is reacted again according to the same protocol with 85 mg of NaH and 176 μl of iodomethane for an additional 2 h. 500 mg of 3-[2-(2-{2-[2-((tert-butoxycarbonyl)(methyl)amino)ethoxy]ethoxy}ethoxy)ethoxy]propanoic acid are thus obtained.

Workup

  1. stirringThe mixture is then stirred at AT for 2 h
  2. waitAfter 12 h at AT
  3. extractionThe aqueous phase is extracted 3× with AcOEt
  4. dry with materialthe combined organic phases are dried over MgSO4
  5. concentrationconcentrated under RP
  6. customthe crude product obtained
  7. customis reacted again

Sources & evidence

ORD record
ord-cd53b5a9991f4787a05fbfb75bda106a
Source dataset
uspto-grants-2013_07
Patent number
US08481042B2

Reaction notes

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