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

HRID 1427385Notes

Reaction equation

HRID 1427385 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]([O:14][CH2:15][CH:16]=[N:17][OH:18])[CH2:11][CH:12]=[CH2:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[O-].[Na+]>ClCCl.O>[CH2:1]([O:8][CH2:9][C@@H:10]1[O:14][CH2:15][C:16]2=[N:17][O:18][CH2:13][C@@H:12]2[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 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 6344DichloromethaneSolvent

Procedure

A solution of 2-{[(2R)-1-(benzyloxy)pent-4-en-2-yl]oxy}-N-hydroxyethanimine (C4) (7.12 g, 28.6 mmol) in dichloromethane (168 mL) was placed in a room temperature water bath. Triethylamine (0.299 mL, 2.14 mmol) was added, followed by addition of bleach (aqueous sodium hypochlorite solution, 6.15%, 71 mL, 59 mmol) at a rate slow enough to maintain the internal reaction temperature between 22° C. and 25.5° C. Upon completion of the addition, the reaction mixture was diluted with water and extracted three times with dichloromethane. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane) provided the product as a yellow 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: 5.65 g, 22.8 mmol, 80%. LCMS m/z 248.1 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.51-1.63 (m, 1H), 2.17-2.24 (m, 1H), 3.40-3.52 (m, 1H), 3.49 (dd, half of ABX pattern, J=10.2, 4.2 Hz, 1H), 3.57 (dd, half of ABX pattern, J=10.2, 5.8 Hz, 1H), 3.68-3.77 (m, 1H), 3.79 (dd, J=11.8, 8.1 Hz, 1H), 4.23 (dd, J=13.5, 1.2 Hz, 1H), 4.54-4.65 (m, 3H), 4.77 (d, J=13.5 Hz, 1H), 7.27-7.39 (m, 5H).

Workup

  1. customwas placed in a room temperature
  2. temperatureto maintain the internal reaction temperature between 22° C. and 25.5° C
  3. additionUpon completion of the addition
  4. extractionextracted three times with dichloromethane
  5. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification via silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-3a180e12cb0f41208293374c1f8542ff
Source dataset
uspto-grants-2015_01
Patent number
US08933221B2

Reaction notes

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