8-Benzyl-3,8-diazabicyclo[3.2.1]octane → 5-{1-hydroxy-2-[8-(phenylmethyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one

HRID 1187044Notes

Reaction equation

[CH3:1][C:2]1[C:10]2[CH2:9][O:8][C:7](=[O:11])[C:6]=2[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:14][O:13]1.[C:15]1([CH2:21][N:22]2[CH:27]3[CH2:28][CH2:29][CH:23]2[CH2:24][NH:25][CH2:26]3)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CS(C)=O.O>[OH:13][CH:12]([C:3]1[CH:4]=[CH:5][C:6]2[C:7](=[O:11])[O:8][CH2:9][C:10]=2[C:2]=1[CH3:1])[CH2:14][N:25]1[CH2:26][CH:27]2[N:22]([CH2:21][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:23]([CH2:29][CH2:28]2)[CH2:24]1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 4-methyl-5-oxiran-2-yl-2-benzofuran-1(3H)-one (1.0 g, 3.7 mmol) and 8-(phenylmethyl)-3,8-diazabicyclo[3.2.1]octane (748 mg, 3.68 mmol) in 2 mL DMSO was heated under microwave condition (150° C.) for 1 hr. After cooling to rt., the mixture was diluted with water (50 mL), extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine and dried over Na2SO4, then concentrated. The residue was purified by TLC (MeOH/DCM=1:15) to obtain 5-{1-hydroxy-2-[8-(phenylmethyl)-3,8-diazabicyclo[3.2.1]oct-3-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one. The two isomers were separated by SFC chiral chromatography to obtain two single isomers, isomer A and isomer B with the same MS m/z 393 (M+1)+.

Workup

temperatureAfter cooling to rt
extractionextracted with EtOAc (3×50 mL)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe residue was purified by TLC (MeOH/DCM=1:15)

Sources & evidence

ORD record: ord-39f10b52c9804ef19c6acb94ef3e716e
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673920B2

Reaction notes

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