Methanol → 1-{[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile

HRID 1423830Notes

Reaction equation

[C:1]1([C@@H:7]2[C@@H:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[O:10][C:9]3([CH2:22][CH2:21][CH2:20][C@H:19]([CH2:23][NH:24][C:25]4[CH:26]=[C:27]([CH:30]=[CH:31][C:32]=4[N+:33]([O-])=O)[C:28]#[N:29])[CH2:18]3)[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[CH:38](OC)(OC)OC>[Fe].C(O)=O.CCOC(C)=O>[C:1]1([C@@H:7]2[C@@H:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[O:10][C:9]3([CH2:22][CH2:21][CH2:20][C@H:19]([CH2:23][N:24]4[C:25]5[CH:26]=[C:27]([C:28]#[N:29])[CH:30]=[CH:31][C:32]=5[N:33]=[CH:38]4)[CH2:18]3)[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 64 °C

Procedure

To a 3 L flask fitted with an overhead stirrer was added 3-({[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.5]dec-7-yl]methyl}amino)-4-nitrobenzonitrile (131 g, 279 mmol), iron (156 g, 2790 mmol), MeOH (1 L), EtOAc (1 L), trimethyl orthoformate (0.308 L, 2790 mmol) and formic acid (0.107 L, 2790 mmol). The mixture was heated to 64° C. Every 15 min an additional 2-3 eq of iron, formic acid and trimethyl orthoformate was added. After 3 h, the solution was cooled to RT and filtered through Celite and washed with EtOAc. The filtrate was concentrated to give 1-{[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile (125 g, 100% yield). MS (m/z) 450.2 (M+H+). The product was used without further purification.

Workup

customTo a 3 L flask fitted with an overhead stirrer
temperaturethe solution was cooled to RT
filtrationfiltered through Celite
washwashed with EtOAc
concentrationThe filtrate was concentrated

Sources & evidence

ORD record: ord-5adf6c86f1164bae92754629eb7be281
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927585B2

Reaction notes

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