Cesium carbonate → (1R,2R,3S,5S)-3-Benzoyloxy-8-(4-cyanonaphthalen-1-yl)-8-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester

HRID 916351Notes

Reaction equation

Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]#[N:13])=[CH:4][CH:3]=1.[CH3:14][O:15][C:16]([C@H:18]1[C@@H:25]([O:26][C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:28])[CH2:24][C@H:22]2[NH:23][C@@H:19]1[CH2:20][CH2:21]2)=[O:17].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:14][O:15][C:16]([C@H:18]1[C@@H:25]([O:26][C:27](=[O:28])[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:24][C@H:22]2[N:23]([C:2]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:5]([C:12]#[N:13])=[CH:4][CH:3]=3)[C@@H:19]1[CH2:20][CH2:21]2)=[O:17]

Participants

Conditions

Temperature: 110 °C

Procedure

Adapting a protocol by Wolfe and Buchwald (Tetrahedron Lett., 1997, 37, 6359-6362), 1-bromo-4-cyanonaphthalene (124 mg, 0.53 mmol, Cakmak O. et al., Collect. Czech. Chem. Commun. 2000, 65, 1791-1804), norcocaine (185 mg, 0.64 mmol), Pd2(dba)3 (23.8 mg, 0.026 mmol), rac-BINAP (24.7 mg, 0.040 mmol) and caesium carbonate (242 mg, 0.74 mmol) were placed in an argon flushed vial, toluene (1.0 mL) was added and the resulting mixture was stirred under argon atmosphere at 110° C. overnight. The crude was then concentrated in vacuo and purification by preparative TLC (ethyl acetate/n-heptane 1:4, 4× eluted) afforded the title compound (68 mg, 29%) as an oil.

Workup

customet al., Collect
concentrationThe crude was then concentrated in vacuo and purification by preparative TLC (ethyl acetate/n-heptane 1:4, 4× eluted)

Sources & evidence

ORD record: ord-da4d955b64a34452a654cc25c6250c4e
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07268232B2

Reaction notes

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