Hydrochloric Acid → HCID 9908569, compound

HRID 973659Notes

Reaction equation

HRID 973659 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2([CH2:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH:29]([CH:32]([C:34]4[NH:38][C:37]5[CH:39]=[CH:40][CH:41]=[CH:42][C:36]=5[N:35]=4)[OH:33])[CH2:28][CH2:27]3)OCC[O:19]2)=[CH:14][CH:13]=1.C(N(CC)CC)C.Cl.C(=O)(O)[O-].[Na+]>ClCCl.CO>[NH:35]1[C:36]2[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=2[N:38]=[C:34]1[C:32]([CH:29]1[CH2:30][CH2:31][N:26]([CH2:25][CH2:24][CH2:23][C:18]([C:15]2[CH:16]=[CH:17][C:12]([F:11])=[CH:13][CH:14]=2)=[O:19])[CH2:27][CH2:28]1)=[O:33]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 19988842HCID 19988842, compound

Product 1

HCID 9908569HCID 9908569, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of oxalyl chloride (0.51 ml, 0.74 g, 5.8 mmol) in dichloromethane (13 ml) at -78° C. under argon was added dimethylsulfoxide (0.91 g, 12 mmol) in dichloromethane (2.5 ml) at such a rate as to keep the temperature below -50° C. After stirring 20 minutes at -78° C., α-[1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-piperidinyl]-lH-benzimidazole-2-methanol (2.3 g, 5.2 mmol) was added in dichloromethane (20 ml), dropwise, via syringe. After an additional 20 minutes of stirring at -78° C., triethylamine (3.0 ml, 22 mmol) was added, the cooling bath was removed, and the solution was allowed to stir for 1 hour. Water was added, the layers separated, and the aqueous layer extracted with dichloromethane. The combined organic layers were dried (MgSO4), and filtered through a pad of silica (eluting with acetone). The eluent was concentrated to give a white foam. The foam was dissolved in methanol (50 ml), treated with 10% hydrochloric acid, and stirred for 3 hours. The solution was neutralized with 5% sodium bicarbonate, concentrated, and extracted twice with dichloromethane. The combined organic layers were dried (MgSO4), concentrated, and the resulting solid recrystallized from ethyl acetate to afford 4-[4-(lH-benzimidazol-2-yl-carbonyl)-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone as an off-white solid m.p. 155-156° C.

Workup

  1. customthe temperature below -50° C
  2. stirringAfter an additional 20 minutes of stirring at -78° C.
  3. customthe cooling bath was removed
  4. stirringto stir for 1 hour
  5. additionWater was added
  6. customthe layers separated
  7. extractionthe aqueous layer extracted with dichloromethane
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. filtrationfiltered through a pad of silica (eluting with acetone)
  10. concentrationThe eluent was concentrated
  11. customto give a white foam
  12. stirringstirred for 3 hours
  13. concentrationconcentrated
  14. extractionextracted twice with dichloromethane
  15. dry with materialThe combined organic layers were dried (MgSO4)
  16. concentrationconcentrated
  17. customthe resulting solid recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-7a430b0574b44cbab1de7c391cdfb470
Source dataset
uspto-grants-1991_11
Patent number
US05064840

Reaction notes

Loading…