2-Methyltetrahydrofuran → tert-butyl 4-[(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-enyl]-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 2284535Notes

Reaction equation

[CH2:1]([N:5]1[CH2:22][CH2:21][CH2:20][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6]1)[CH2:2][C:3]#[CH:4].CC1CCCO1.[CH3:29][C:30]1([CH3:37])[C:34]([CH3:36])([CH3:35])[O:33][BH:32][O:31]1>[Cl-].[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Zr+2].C(N(CC)CC)C.ClCCl>[CH3:29][C:30]1([CH3:37])[C:34]([CH3:36])([CH3:35])[O:33][B:32](/[CH:4]=[CH:3]/[CH2:2][CH2:1][N:5]2[CH2:6][C:7]3([CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[O:14])[CH2:11][CH2:12]3)[CH2:20][CH2:21][CH2:22]2)[O:31]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of tert-butyl 8-but-3-ynyl-3,8-diazaspiro[5.5]undecane-3-carboxylate (2.41 moles; 750.86 g), zirconocene chloride (240.73 mmoles; 62.08 g), triethylamine (240.73 mmoles; 33.55 mL; 24.36 g), and 2-methyltetrahydrofuran (738 mL), add 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.53 moles; 323.49 g). Heat the mixture to 60° C. and stir overnight. Cool the mixture and pass through a plug of silica eluting with dichloromethane. Concentrate the filtrate under reduced pressure to give the final title compound, tert-butyl 4-[(E)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-enyl]-4,9-diazaspiro[5.5]undecane-9-carboxylate (1072 g, about 94% purity, 96% yield).

Workup

concentrationConcentrate the filtrate under reduced pressure

Sources & evidence

ORD record: ord-e0e796306fe9427fa813d3e0e18cf170
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09145435B2

Reaction notes

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