Réaction #554670

Équation de réaction

Diisopropyl azodicarboxylate

(4-benzyl-3-methyl-1,4-oxazepan-6-yl)methanol

4-fluoro-3-methylphenol

→

4-benzyl-6-[(4-fluoro-3-methylphenoxy)methyl]-3-methyl-1,4-oxazepane

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   Filtrationfiltered
2. 2
   ConcentrationThe filtrate was concentrated
3. 3
   Autrethe residue was purified by flash column chromatography (20% EtOAc in hexanes)

Mode opératoire

Diisopropyl azodicarboxylate (40 uL, 0.20 mmol, 1.2 equiv) was added to a suspension of (4-benzyl-3-methyl-1,4-oxazepan-6-yl)methanol (4-5, 40 mg, 0.17 mmol, 1 equiv), 4-fluoro-3-methylphenol (26 mg, 0.20 mmol, 1.2 equiv), and polystyrene-supported triphenylphosphine resin (250 mg, 0.51 mmol, 3.0 equiv) in anhydrous dichloromethane (30 mL) at 23° C. The mixture was stirred for 20 h, then filtered. The filtrate was concentrated and the residue was purified by flash column chromatography (20% EtOAc in hexanes) to provide 4-benzyl-6-[(4-fluoro-3-methylphenoxy)methyl]-3-methyl-1,4-oxazepane (4-6) as a ˜1:1 mixture of diastereomers (colorless oil). 1H NMR (300 MHz, CDCl3, reported for a single diasteromer) δ 7.38-7.19 (m, 5H), 6.85 (ddd, 1H,J=12.5, 9.2, 3.7 Hz), 6.53 (m, 2H), 3.97-3.50 (m, 6H), 3.08 (m, 1H), 3.00 (dd, 1H,J=14.0, 4.0 Hz), 2.90 (d, 1H,J=13.7 Hz), 2.82 (dd, 1H,J=14.0, 3.0 Hz), 2.60 (d, 1H,J=13.7 Hz), 2.44 (m, 1H), 2.21 (s w/small splittings, 3H), 1.08 (d, 3H,J=6.7 Hz). LRMS m/z (M+H) 344.4 found, 344.2 required.

Source