Triethylamine → (3S,3aR,5R)-5-[(benzyloxy)methyl]-3-methyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole

HRID 590606Notes

Reaction equation

HRID 590606 reaction equation
Cl[O-].[Na+].[CH2:4]([O:11][CH2:12][C@H:13]([O:18][CH2:19][CH:20]=[N:21][OH:22])[CH2:14][CH:15]=[CH:16][CH3:17])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(CC)CC)C>ClCCl>[CH2:4]([O:11][CH2:12][C@@H:13]1[O:18][CH2:19][C:20]2=[N:21][O:22][C@@H:16]([CH3:17])[C@@H:15]2[CH2:14]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 23665760Sodium HypochloriteHCID 867010832-{[(2R)-1-(benzyloxy)hex-4-en-2-yl]oxy}-N-hydroxyethanimine

Product 1

HCID 86701084(3S,3aR,5R)-5-[(benzyloxy)methyl]-3-methyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

An aqueous solution of sodium hypochlorite (6.15% solution, 6.6 L) was slowly added to a solution of 2-{[(2R)-1-(benzyloxy)hex-4-en-2-yl]oxy}-N-hydroxyethanimine (C15) (660 g, 2.51 mol) and triethylamine (19 g, 0.19 mol) in dichloromethane (6.6 L) at 25° C. After completion of the addition, the reaction mixture was stirred at 25° C. for 30 minutes. The organic layer was washed with water (3×3 L), dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via chromatography on silica gel (Eluent: ethyl acetate in petroleum ether) provided (3S,3aR,5R)-5-[(benzyloxy)methyl]-3-methyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole (C16) as a white solid. Yield: 90 g, 0.34 mol, 14%. The indicated relative stereochemistry of compound C16 was assigned based on nuclear Overhauser enhancement studies, which revealed interactions of the methine proton on carbon 3a with both the protons of the methyl group on carbon 3 and the methine proton on carbon 5. LCMS m/z 261.9 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 7.24-7.39 (m, 5H), 4.69 (d, J=13.7 Hz, 1H), 4.57 (AB quartet, JAB=12.2 Hz, ΔνAB=13.8 Hz, 2H), 4.13-4.25 (m, 2H), 3.62-3.70 (m, 1H), 3.55 (dd, half of ABX pattern, J=10, 6 Hz, 1H), 3.47 (dd, half of ABX pattern, J=10, 4 Hz, 1H), 2.93 (br ddd, J=11, 11, 7 Hz, 1H), 2.11 (br dd, J=12.6, 6.8 Hz, 1H), 1.45-1.56 (m, 1H), 1.45 (d, J=6.2 Hz, 3H).

Workup

  1. additionAfter completion of the addition
  2. washThe organic layer was washed with water (3×3 L)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification via chromatography on silica gel (Eluent: ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-decc22653db5413f998dcb572b4e89ca
Source dataset
uspto-grants-2016_01
Patent number
US09233981B1

Reaction notes

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