Triethylamine → (2-{2-[2-((2R,3R,4R,5R,6R)-4,5-Diacetoxy-6-acetoxymethyl-3-acetylamino-tetrahydro-pyran-2-yloxy)-ethoxy]-ethoxy}-ethoxy)-acetic acid benzyl ester

HRID 526279Notes

Reaction equation

HRID 526279 reaction equation
[C:1]([O:4][C@H:5]1[C@@H:13]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:12][C@H:11]2[C@H:7]([N:8]=[C:9]([CH3:19])[O:10]2)[C@H:6]1[O:20][C:21](=[O:23])[CH3:22])(=[O:3])[CH3:2].[CH2:24]([O:31][C:32](=[O:44])[CH2:33][O:34][CH2:35][CH2:36][O:37][CH2:38][CH2:39][O:40][CH2:41][CH2:42][OH:43])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(N(CC)CC)C>C(Cl)Cl>[CH2:24]([O:31][C:32](=[O:44])[CH2:33][O:34][CH2:35][CH2:36][O:37][CH2:38][CH2:39][O:40][CH2:41][CH2:42][O:43][C@H:11]1[C@H:7]([NH:8][C:9](=[O:10])[CH3:19])[C@@H:6]([O:20][C:21](=[O:23])[CH3:22])[C@@H:5]([O:4][C:1](=[O:3])[CH3:2])[C@@H:13]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:12]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65367Trimethylsilyl triflateHCID 11278902(3aR,5R,6R,7R,7aR)-5-(acetoxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazole-6,7-diyl diacetateHCID 58409191Benzyl 2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)acetate

Product 1

HCID 58409195(2-{2-[2-((2R,3R,4R,5R,6R)-4,5-Diacetoxy-6-acetoxymethyl-3-acetylamino-tetrahydro-pyran-2-yloxy)-ethoxy]-ethoxy}-ethoxy)-acetic acid benzyl esterYield 96.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The above prepared acetic acid (3aR,5R,6R,7R,7aR)-6-acetoxy-5-acetoxymethyl-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazol-7-yl ester (10.3 g, 26 mmol) and {2-[2-(2-hydroxy-ethoxy)-ethoxy]-ethoxy}-acetic acid benzyl ester (8.62 g, 29 mmol) were mixed in 520 ml, of CH2Cl2 and treated with 63 g of 4 Angstrom molecular sieves. After 1 h trimethylsilyl triflate (6.13 g, 28 mmol) was added. The reaction mixture was stirred over the weekend at ambient temperature. Triethylamine (5.21 ml, 37 mmol) was added, the molecular sieves filtered off, the filtrate diluted with CH2Cl2 and washed with NaHCO3-solution and water. Drying over Na2SO4 and evaporation of the solvent followed by flash chromatography (SiO2, ethyl acetate/AcOH/MeOH/water=60/3/3/2) afforded 15.7 g of the title compound as a brownish oil. MS (ISP): 626.6 [M−H]−.

Workup

  1. additiontreated with 63 g of 4 Angstrom molecular sieves
  2. filtrationthe molecular sieves filtered off
  3. additionthe filtrate diluted with CH2Cl2
  4. washwashed with NaHCO3-solution and water
  5. dry with materialDrying over Na2SO4 and evaporation of the solvent

Sources & evidence

ORD record
ord-046238313a364c9f9f9e29b1a3fa663e
Source dataset
uspto-grants-2016_05
Patent number
US09345775B2

Reaction notes

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