Decylamine → 2-(3-{2-[2-(2-{2-Azidoethoxy}ethoxy)ethoxy]ethoxy}-4,5-dimethoxyphenyl)-1,3-dioxolane

HRID 1510976Notes

Reaction equation

HRID 1510976 reaction equation
O1C2C=CC(C3C(=O)OC(O)(C4C=CC(OC)=CC=4)C=3[CH2:15][C:16]3[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[C:18]([O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][N:38]=[N+:39]=[N-:40])[CH:17]=3)=CC=2OC1.CCCCCCCCCCN.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[O:82][C:83]1C(OC)=CC(C=O)=C[C:84]=1[OH:93].N(CCOCCOCCOCCOC1C=C(C=C(OC)C=1OC)C=O)=[N+]=[N-]>C1COCC1.C(O)CO.O>[N:38]([CH2:37][CH2:36][O:35][CH2:34][CH2:33][O:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27][O:26][C:18]1[CH:17]=[C:16]([CH:15]2[O:93][CH2:84][CH2:83][O:82]2)[CH:21]=[C:20]([O:22][CH3:23])[C:19]=1[O:24][CH3:25])=[N+:39]=[N-:40]

Participants

9

Reactant 5

HCID 8916DecylamineHCID 11776TriphenylphosphineHCID 1415133,4-Dimethoxy-5-hydroxybenzaldehydeHCID 866321203-Benzo[1,3]dioxol-5-yl-4-(3-(2-{2-[2-(2-azidoethoxy)ethoxy]ethoxy}ethoxy)-4,5-dimethoxybenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H-furan-2-oneHCID 866321223-{2-[2-(2-{2-Azidoethoxy}ethoxy)ethoxy]ethoxy}-4,5-dimethoxybenzaldehyde

Product 1

HCID 866321212-(3-{2-[2-(2-{2-Azidoethoxy}ethoxy)ethoxy]ethoxy}-4,5-dimethoxyphenyl)-1,3-dioxolane

Reagents, catalysts & solvents 3

HCID 174Ethylene GlycolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Compound 9 is then converted to the free amine 10 by Staudinger-Reaction with triphenylphosphine and water in THF (scheme 3). Regrettably, the yields in this step were disappointing (<20%) and several byproducts made the purification rather difficult. This probably occurred due to reaction of the phosphine with one of the oxygen-containing moieties of the butenolide ring structure. To circumvent these difficulties a second reaction sequence was chosen, where the amine was generated earlier and then protected for further conversion. This second sequence (scheme 4) also starts with the reaction of 3,4-dimethoxy-5-hydroxybenzaldehyde 1 with PEG-derivative 7. The aldehyde function of azide 8 is then protected with ethylene glycol, giving dioxolane 11 in nearly quantitative yield after purification. This kind of protection allows subsequent reduction of the azide and BOC protection of the generated amine 12 without the risk of intermolecular imine formation. The dioxolane protecting group of 13 then can easily be destroyed by reaction with catalytic amounts of iodine in acetone without affecting the BOC protecting group. The product benzaldehyde 14 and ketoester 3 are then converted to the desired butenolide derivative by the same procedure as described above for the azide functionalised aldehyde 8 (scheme 3). The product of this rection is the PEG-modified, N-Boc-protected butenolide 15, which in the finishing step is deprotected by treatment with trifluoroacetic acid (TFA) in methylene chloride. The final product 16 can be isolated as the TFA salt which can be handled and stored easily at 4° C.

Workup

  1. customRegrettably, the yields in this step
  2. customthe purification rather difficult
  3. customThis probably occurred due to reaction of the phosphine with one of the oxygen-
  4. additioncontaining moieties of the butenolide ring structure

Sources & evidence

ORD record
ord-e5f7214afcf244f7b38266223393fa70
Source dataset
uspto-grants-2012_07
Patent number
US08212058B2

Reaction notes

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