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

HRID 1496734Notes

Reaction equation

HRID 1496734 reaction equation
N1C=CC=CC=1.[CH2:7]([O:14][CH2:15][C@H:16]([O:20][CH2:21][CH:22]=[N:23][OH:24])[CH2:17][CH:18]=[CH2:19])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.ClN1C(=O)CCC1=O>ClCCl.S([O-])([O-])=O.[Na+].[Na+]>[CH2:7]([O:14][CH2:15][C@@H:16]1[O:20][CH2:21][C:22]2=[N:23][O:24][CH2:19][C@@H:18]2[CH2:17]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 31398ChlorosuccinimideHCID 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 6344DichloromethaneSolventHCID 24437Sodium SulfiteSolvent

Procedure

Pyridine (23.1 mL, 286 mmol) was added to a solution of 2-{[(2R)-1-(benzyloxy)pent-4-en-2-yl]oxy}-N-hydroxyethanimine (C3) (35.6 g, 143 mmol) in dichloromethane (350 mL). N-Chlorosuccinimide (19.4 g, 145 mmol) was added in portions over roughly 2 hours. The reaction was stirred for 3 hours, then diluted with an aqueous solution of sodium sulfite (5 g in 100 mL water). The mixture was stirred for 20 minutes, and the aqueous layer was extracted with dichloromethane; the combined organic layers were washed with water, dried, and concentrated. Purification via silica gel chromatography (Eluent: 1:2 ethyl acetate/hexanes) afforded the product. Yield: 21.2 g, 85.7 mmol, 60%. 1H NMR (400 MHz, CDCl3) δ 7.28-7.40 (m, 5H), 4.77 (d, J=13.4 Hz, 1H), 4.55-4.65 (m, 3H), 4.22 (dd, J=13.5, 1.3 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=10.2, 5.9 Hz, 1H), 3.49 (dd, half of ABX pattern, J=10.2, 4.3 Hz, 1H), 3.40-3.5 (m, 1H), 2.21 (ddd, J=12.9, 6.5, 1.8 Hz, 1H), 1.57 (ddd, J=13, 12, 11 Hz, 1H).

Workup

  1. stirringThe mixture was stirred for 20 minutes
  2. extractionthe aqueous layer was extracted with dichloromethane
  3. washthe combined organic layers were washed with water
  4. customdried
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography (Eluent: 1:2 ethyl acetate/hexanes)
  7. customafforded the product

Sources & evidence

ORD record
ord-2eac7a66d3694685ab823b20ad6fc15e
Source dataset
uspto-grants-2015_12
Patent number
US09198917B2

Reaction notes

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