Ammonium formate → (4-Fluoro-1-tetrahydropyran-2-yl-benzimidazol-5-yl)methanamine

HRID 475231Notes

Reaction equation

HRID 475231 reaction equation
[F:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[CH:17]=[N:18]O.C([O-])=O.[NH4+]>CO.[Zn]>[F:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:17][NH2:18]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 866947334-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde oxime

Product 1

HCID 86694734(4-Fluoro-1-tetrahydropyran-2-yl-benzimidazol-5-yl)methanamineYield 47.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 150 (5.8 g, 0.022 mol) in MeOH (100 mL) was added zinc dust (2.9 g, 0.044 mol) and ammonium formate (2.8 g, 0.044 mol). The resulting mixture was heated to 75° C. for 2 h. The mixture was filtered through a Celite® pad. The filtrate was concentrated and the crude product was purified by SiO2 chromatography eluting with 5% MeOH/DCM to afford 2.6 g (47%) of (4-fluoro-1-tetrahydropyran-2-yl-benzimidazol-5-yl)methanamine (152) as a yellow solid: 1H-NMR (400 MHz, RT, CDCl3): δ 1.66-1.80 (m, 3H), 1.92-1.96 (m, 1H), 2.06-2.14 (m, 2H), 3.68-3.74 (m, 1H), 4.23-4.26 (m, 1H), 4.40 (br, 2H), 5.49-5.52 (dd, 1H), 6.94-6.99 (dd, 1H), 7.18-7.23 (t, 1H), and 7.37-7.39 (d, 1H); MS (ESI) m/z=250.2 [M+1]+.

Workup

  1. filtrationThe mixture was filtered through a Celite® pad
  2. concentrationThe filtrate was concentrated
  3. customthe crude product was purified by SiO2 chromatography
  4. washeluting with 5% MeOH/DCM

Sources & evidence

ORD record
ord-7cc31387f4a1417bb5ceb9d19b2ef9da
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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