Dimethyl Sulfoxide → 3-Benzyl-3-azabicyclo[3.1.0]hexane-6-carbaldehyde

HRID 2079778Notes

Reaction equation

C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([N:18]1[CH2:23][CH:22]2[CH:20]([CH:21]2[CH2:24][OH:25])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[CH2:11]([N:18]1[CH2:23][CH:22]2[CH:20]([CH:21]2[CH:24]=[O:25])[CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

Conditions

Temperature: -65 °C

Procedure

Oxalyl chloride (0.88 ml, 17.73 mmol) was added to a stirred flask of DCM (100 ml) under N2 and the solution cooled to an internal temperature of −65° C. DMSO (1.26 ml, 17.73 mmol) was then added dropwise, keeping the internal temperature at −65° C. or below at all times. A solution of (3-benzyl-3-azabicyclo[3.1.0]hex-6-yl)methanol (2.00 g, 9.85 mmol) in DCM (50 ml) was then added to the reaction mixture slowly, again making sure the internal temperature did not rise above −65° C. After this addition was complete, triethylamine (5.90 ml, 42.35 mmol) was slowly added to the reaction, again making sure the internal temperature did not rise above −65° C. After addition was complete the reaction was allowed to warm up to r.t. and solvent removed in vacuo. The residue was purified by column chromatography (25% EtOAc in heptane) to give the title compound as a light yellow oil (1.49 g, 76%). LCMS purity 90%, m/z 202 [M+H]+, 1H NMR (300 MHz, d6-DMSO) δ: 2.11 (2H, m), 2.44 (1H, m), 2.50 (2H, d, J=9.3 Hz), 3.07 (2H, d, J=9.3 Hz), 3.64 (2H, s), 7.21-7.35 (5H, m), 9.31 (1H, d, J=4.8 Hz).

Workup

customat −65° C. or below
customdid not rise above −65° C
additionAfter this addition
customdid not rise above −65° C
additionAfter addition
temperatureto warm up to r.t.
customsolvent removed in vacuo
customThe residue was purified by column chromatography (25% EtOAc in heptane)

Sources & evidence

ORD record: ord-20d65823b8ee44839fa8a5dd73b8f1a9
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07932246B2

Reaction notes

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