Tetrahydrofuran → HCID 10868317, compound

HRID 1507473Notes

Reaction equation

HRID 1507473 reaction equation
C1COCC1.[Cl:6][C:7]1[NH:8][C:9]2[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=2[N:11]=1.[O:16]1[CH:21]=[CH:20][CH2:19][CH2:18][CH2:17]1.C[O-].[Na+]>C1(C)C=CC(S(O)(=O)=O)=CC=1.CCCCCCC>[Cl:6][C:7]1[N:11]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21][O:16]2)[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[N:8]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 80803,4-dihydro-2H-pyranHCID 785722-ChlorobenzimidazoleHCID 10942334Sodium Methoxide

Product 1

HCID 10868317HCID 10868317, compoundYield 104.8%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 8900HeptaneSolvent

Procedure

A 10 l reactor is charged, under argon and with stirring, with 2.5 l of THF, 180 g of 2-chlorobenzimidazole (1.18 mol) and 325 ml of 3,4-dihydro-2H-pyran (6.56 mol, 3 eq.). The reactor is heated until dissolution occurs (temperature of the mixture: 40° C.). Then 6.3 g of para-toluenesulphonic acid (0.033 mol, 0.028 eq.) are introduced. The temperature is held at between 49 and 52° C. for 2.5 h. Cooling takes place at 12° C. and 7.65 g of sodium methoxide (0.142 mol, 0.12 eq.) are added, with stirring maintained for a total time of 15 min. The temperature is then taken to 18° C., 5 l of n-heptane are added, and the whole mixture is filtered on 300 g of Clarcel FLO-M, the retentate being washed with 5 l of n-heptane. The filtrate is concentrated to dryness under reduced pressure to give 292.6 g of 2-chloro-1-(tetrahydro-pyran-2-yl)-1H-benzimidazole in the form of a slightly yellow oil (quantitative yield). 1H NMR (400 MHz, DMSO-d6): 1.42 to 2.01 (m, 5H); 2.21 to 2.34 (m, 1H); 3.69 to 3.78 (m, 1H); 4.12 (d, J=11.4 Hz, 1H); 5.72 (dd, J=2.4 and 11.2 Hz, 1H); 7.22 to 7.34 (m, 2H); 7.82 (d. J=72 Hz, 1H); 7.78 (d, J=7.2 Hz, 1H).

Workup

  1. additionA 10 l reactor is charged, under argon
  2. temperatureThe reactor is heated until dissolution
  3. custom40° C.
  4. temperatureCooling
  5. customat 12° C.
  6. temperaturemaintained for a total time of 15 min
  7. customis then taken to 18° C.
  8. filtrationthe whole mixture is filtered on 300 g of Clarcel FLO-M
  9. washthe retentate being washed with 5 l of n-heptane
  10. concentrationThe filtrate is concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-72d95124dc234b209889ae9f809bced2
Source dataset
uspto-grants-2015_12
Patent number
US09221817B2

Reaction notes

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