Acetic Acid → diethyl (((2S,4R,5S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-3-(hydroxyimino)tetrahydro-2H-pyran-2-yl)methyl)phosphonate

HRID 522186Notes

Reaction equation

HRID 522186 reaction equation
[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([CH2:23][O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:12][C@H:11]([CH2:32][P:33](=[O:40])([O:37][CH2:38][CH3:39])[O:34][CH2:35][CH3:36])[C:10]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[Na])(C)=O.[OH2:47].O.O.[NH2:50]O.Cl.C(O)(=O)C>C1COCC1.CO>[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([CH2:23][O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:12][C@H:11]([CH2:32][P:33](=[O:40])([O:37][CH2:38][CH3:39])[O:34][CH2:35][CH3:36])[C:10]1=[N:50][OH:47])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 443297Hydroxyamine hydrochlorideHCID 131735510diethyl (((2 S,4S,5R,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-3-oxotetrahydro-2H-pyran-2-yl)methyl)phosphonateHCID 178476686sodium;acetate;trihydrate

Product 1

HCID 131735509diethyl (((2S,4R,5S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-3-(hydroxyimino)tetrahydro-2H-pyran-2-yl)methyl)phosphonateYield 74%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of diethyl (((2 S,4S,5R,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-3-oxotetrahydro-2H-pyran-2-yl)methyl)phosphonate (1.3 g, 2.23 mmol, 1.0 equiv) in THF/MeOH (42 mL, 1:1) was treated with a buffer solution (17.68 mL) prepared with 15 g of AcONa.3H2O and 7.5 g of NH2OH.HCl. The pH was then adjusted to 4.5 by dropwise addition of acetic acid. After 1 hour, the mixture was extracted with DCM (3×30 mL), and the organic layer was washed sequentially with water (50 mL), saturated aqueous sodium bicarbonate solution (75 mL) and finally with water to neutrality. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The product thus obtained was purified by silica gel chromatography, eluting with 60% EtOAc in hexane to give diethyl (((2S,4R,5S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-3-(hydroxyimino)tetrahydro-2H-pyran-2-yl)methyl)phosphonate (0.98 g, 74%) as a mixture of E and Z isomers as a white solid. NMR data refers to the more abundant isomer. 1H NMR (400 MHz, DMSO-d6) δ 11.36 (d, J=1.1 Hz, 1H), 7.39-7.25 (m, 13H), 7.21 (dd, J=7.6, 2.0 Hz, 2H), 5.21 (td, J=10.6, 3.2 Hz, 1H), 4.73 (d, J=12.0 Hz, 1H), 4.64 (d, J=11.5 Hz, 1H), 4.57-4.47 (m, 4H), 4.40 (d, J=6.6 Hz, 1H), 4.04-3.91 (m, 5H), 3.71 (t, J=6.0 Hz, 1H), 3.60 (dd, J=10.1, 4.9 Hz, 1H), 3.53 (dd, J=10.2, 4.7 Hz, 1H), 2.70-2.53 (m, 1H), 2.11 (ddd, J=19.4, 15.7, 3.8 Hz, 1H), 1.19 (qd, J=7.1, 1.1 Hz, 6H). ESI (M+1) 598.0; calc for C32H40NO8P 597.3.

Workup

  1. extractionthe mixture was extracted with DCM (3×30 mL)
  2. washthe organic layer was washed sequentially with water (50 mL), saturated aqueous sodium bicarbonate solution (75 mL) and finally with water to neutrality
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe product thus obtained
  7. customwas purified by silica gel chromatography
  8. washeluting with 60% EtOAc in hexane

Sources & evidence

ORD record
ord-9cb0bc23030349928604de4618bf4a45
Source dataset
uspto-grants-2016_05
Patent number
US09328134B2

Reaction notes

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