Hydrochloric Acid → 1-(1-(phenylmethyl)-4-piperidinyl)-1H-benzimidazole

HRID 1068153Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:16]([NH2:21])=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH:23](OC)(OC)OC>CCOC(C)=O>[CH2:1]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:21]=[CH:23]2)[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 200 mg of N-(1-benzyl-piperidin-4-yl)-benzene-1,2-diamine (from Step A) in 6 mL of trimethyl orthoformate was added 0.2 mL concentrated HCl. After stirring at 80° C. for 16 hours, the reaction mixture was diluted with 30 ml of EtOAc. The organic phase was washed with 15 mL saturated NaHCO3 aqueous solution. After separating layers, the aqueous phase was extracted with 2×20 mL EtOAc. The combined organic phases were washed with 10 mL of brine, dried over MgSO4 and concentrated under reduced pressure to give 198 mg yellow solid. 1H NMR (400 MHz, CDCl3): δ2.11-2.22 (m, 6H), 3.06 (m, 2H), 3.58(s, 2H), 4.20 (s, 1H), 7.24-7.34(m, 7H),7.42(m, 1H), 7.81 (m, 1H), 8.04(s, 1H). ESI-MS 292 (M+H); HPLC A: 1.80 min.

Workup

washThe organic phase was washed with 15 mL saturated NaHCO3 aqueous solution
customAfter separating layers
extractionthe aqueous phase was extracted with 2×20 mL EtOAc
washThe combined organic phases were washed with 10 mL of brine
dry with materialdried over MgSO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-6f12b931d34341179a7291861e892463
Source dataset: uspto-grants-2001_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06248755B1

Reaction notes

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