Acetic Acid → HCID 57455743, compound

HRID 660889Notes

Reaction equation

HRID 660889 reaction equation
[NH:1]1CCCC[CH2:2]1.[Cl:7][C:8]1[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:13]=[CH:12][C:9]=1C=O.[BH4-].C([N+](CCCC)(CCCC)CCCC)CCC.C(O)(=[O:40])C.CN([CH:45]=[O:46])C>>[F:17][C:16]([F:19])([F:18])[C:45]([O-:46])=[O:40].[Cl:7][C:8]1[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:13]=[CH:12][C:9]=1[NH2+:1][CH3:2]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 8082PiperidineHCID 169536Tetrabutylammonium borohydrideHCID 27366722-Chloro-3-(trifluoromethyl)benzaldehyde

Product 1

HCID 57455743HCID 57455743, compound

Procedure

1.75 g of Rink-Amid® (0.96 mmol) is activated (FMOC cleavage) by stirring with 10 ml of a 25% solution of piperidine in DMF for 30 mins, then filtration of the resin and renewed treatment with 10 ml of a 25% solution of piperidine in DMF for 30 mins. The polymer is filtered off at the pump, washed successively three times each with DMF, methanol and dichloromethane and then allowed to swell in 10 ml of trimethyl orthoformate (TMOF). 400 mg (1.9 mmol) of 2-chloro-3-(trifluoromethyl)benzaldehyde are added and the suspension stirred for 5 hrs. The polymer is then filtered off, washed successively three times each with DMF, methanol and dichloromethane and dried on the rotary evaporator. The polymer is again allowed to preswell in 10 ml TMOF, then 987 mg (3.84 mmol) tetrabutylammonium borohydride are added and, slowly, 878 μl (15 mmol) of acetic acid. The suspension is stirred overnight at RT. The polymer is filtered off at the pump and washed successively five times each with DMF, methanol and dichloromethane. Next it is stirred with 20 ml trifluoroacetic acid/dichloromethane (1:1). After 1 hr, the polymer is filtered off at the pump and washed with dichloromethane. The filtrate is freed of the volatile components on the rotary evaporator and the residue briefly dried under high vacuum. 170 mg (27% of theory) of the title compound in acceptable purity (>50%), which is further used in this form, are obtained.

Workup

  1. filtrationfiltration of the resin
  2. customfor 30 mins
  3. filtrationThe polymer is filtered off at the pump
  4. washwashed successively three times each with DMF, methanol and dichloromethane
  5. filtrationThe polymer is then filtered off
  6. washwashed successively three times each with DMF, methanol and dichloromethane
  7. customdried on the rotary evaporator
  8. stirringThe suspension is stirred overnight at RT
  9. filtrationThe polymer is filtered off at the pump
  10. washwashed successively five times each with DMF, methanol and dichloromethane
  11. stirringNext it is stirred with 20 ml trifluoroacetic acid/dichloromethane (1:1)
  12. waitAfter 1 hr
  13. filtrationthe polymer is filtered off at the pump
  14. washwashed with dichloromethane
  15. customThe filtrate is freed of the volatile components on the rotary evaporator
  16. customthe residue briefly dried under high vacuum
  17. customare obtained

Sources & evidence

ORD record
ord-128f4fb550b249469cea366323b71afc
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Reaction notes

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