Sodium Hypochlorite → (3AR,5R)-5-((benzyloxy)methyl)-3a,4,5,7-tetrahydro-3H-pyrano[3,4-c]isoxazole

HRID 68389

Reaction equation

HRID 68389 reaction equation
Cl[O-].[Na+].[CH2:4]([O:11][CH2:12][C@H:13]([O:17][CH2:18][CH:19]=[N:20][OH:21])[CH2:14][CH:15]=[CH2:16])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>ClCCl.O>[CH2:4]([O:11][CH2:12][C@@H:13]1[O:17][CH2:18][C:19]2=[N:20][O:21][CH2:16][C@@H:15]2[CH2:14]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 2

HCID 23665760Sodium HypochloriteHCID 86640913((R)-1-benzyloxymethyl-3-butenyloxy)acetaldehyde oxime

Product 1

HCID 57475687(3AR,5R)-5-((benzyloxy)methyl)-3a,4,5,7-tetrahydro-3H-pyrano[3,4-c]isoxazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

An aqueous solution of sodium hypochlorite (14.5% solution, 600 mL) was added drop-wise to a 0° C. solution of 2-{[(2R)-1-(benzyloxy)pent-4-en-2-yl]oxy}-N-hydroxyethanimine (C3) (224 g from the previous step, ≦0.759 mol) in dichloromethane (1 L), while the internal temperature was maintained below 15° C. After completion of the addition, the reaction mixture was left to stir at 0° C. for 1.5 hours, then diluted with water (1 L) and dichloromethane (500 mL). The aqueous layer was extracted with dichloromethane (2×500 mL), and the combined organic layers were washed with saturated aqueous sodium chloride solution (500 mL), water (500 mL) and again with saturated aqueous sodium chloride solution (500 mL). They were subsequently dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 25% ethyl acetate in heptane) afforded the product as a colorless oil. The indicated relative stereochemistry of compound P1 was assigned based on nuclear Overhauser enhancement studies, which revealed an interaction between the methine protons on carbons 3a and 5. Yield: 85.3 g, 345 mmol, 45% over 2 steps. LCMS m/z 248.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 7.27-7.40 (m, 5H), 4.77 (d, J=13.5 Hz, 1H), 4.54-4.65 (m, 3H), 4.22 (dd, J=13.5, 1 Hz, 1H), 3.79 (dd, J=11.7, 8.0 Hz, 1H), 3.69-3.76 (m, 1H), 3.57 (dd, half of ABX pattern, J=10.1, 5.9 Hz, 1H), 3.49 (dd, half of ABX pattern, J=10.1, 4.3 Hz, 1H), 3.39-3.5 (m, 1H), 2.20 (ddd, J=12.9, 6.5, 1.6 Hz, 1H), 1.51-1.62 (m, 1H).

Workup

  1. temperaturewhile the internal temperature was maintained below 15° C
  2. additionAfter completion of the addition
  3. waitthe reaction mixture was left
  4. extractionThe aqueous layer was extracted with dichloromethane (2×500 mL)
  5. washthe combined organic layers were washed with saturated aqueous sodium chloride solution (500 mL), water (500 mL) and again with saturated aqueous sodium chloride solution (500 mL)
  6. dry with materialThey were subsequently dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification via silica gel chromatography (Gradient: 0% to 25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-c8a00d29d608498b9fbf04aaf8008a2e
Source dataset
uspto-grants-2014_09
Patent number
US08822456B2

Linked notes

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