Azobisisobutyronitrile → (S)-5-tert-Butyl 6-methyl 5-azaspiro[2.4]heptane-5,6-dicarboxylate

HRID 1424672Notes

Reaction equation

Br[C:2]1(Br)[C:4]2([CH2:8][C@@H:7]([C:9]([O:11][CH3:12])=[O:10])[N:6]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:5]2)[CH2:3]1.C[Si]([SiH]([Si](C)(C)C)[Si](C)(C)C)(C)C.CC(N=NC(C#N)(C)C)(C#N)C>C1(C)C=CC=CC=1>[CH2:3]1[C:4]2([CH2:8][C@@H:7]([C:9]([O:11][CH3:12])=[O:10])[N:6]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:5]2)[CH2:2]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of (6S)-5-tert-butyl 6-methyl 1,1-dibromo-5-azaspiro[2.4]heptane-5,6-dicarboxylate (0.209 g, 0.506 mmol) in toluene (5 mL) was added tris(trimethylsilyl)-silane (0.47 mL, 1.518 mmol, 3.0 eq), followed by AIBN (8.3 mg, 0.0506 mmol, 0.1 eq). The mixture was degassed at 0° C. 3 times and then heated at 90° C. for 24 hours. The mixture was allowed to cool down and directly purified by flash column chromatography (silica, Hexanes-EtOAc) to afford the desired product as a colorless oil (89.1 mg, 69%). 1H NMR (500 MHz, CDCl3): 4.36 (dd, J=3.8, 8.4 Hz, 0.4H), 4.25 (dd, J=4.8, 8.3 Hz, 0.6H), 3.62 (s, 3H), 3.30-3.17 (m, 2H), 2.16-2.08 (m, 1H), 1.75 (dd, J=4.7, 12.7 Hz, 0.6H), 1.67 (dd, J=3.8, 12.7 Hz, 0.4H), 1.34/1.31 (two overlapping s, 9H), 0.54-0.39 (m, 4H).

Workup

customThe mixture was degassed at 0° C
temperatureto cool down
customdirectly purified by flash column chromatography (silica, Hexanes-EtOAc)

Sources & evidence

ORD record: ord-bd63052111f14d8b9d0d9d15249cf718
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927739B2

Reaction notes

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