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

HRID 715494Notes

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
washwashed with EtOAc
concentrationThe filtrate was concentrated

Sources & evidence

ORD record: ord-dd9bdf5ed6b347149a809dd5f860e2bd
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187464B2

Reaction notes

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