Cyclopropanecarboxaldehyde → HCID 11283992, compound

HRID 1788286Notes

Reaction equation

HRID 1788286 reaction equation
[Cl:1][C:2]1[C:40]([Cl:41])=[CH:39][C:5]2[NH:6][C:7]([O:9][CH:10]([C:19]3([C:25]4[CH:30]=[CH:29][C:28]([C:31]5[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=5)=[CH:27][CH:26]=4)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)COCC[Si](C)(C)C)=[N:8][C:4]=2[CH:3]=1.[CH:42]1([CH:45]=O)[CH2:44][CH2:43]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>ClCCCl.O1CCCC1.C(O)(=O)C>[CH:42]1([CH2:45][N:22]2[CH2:23][CH2:24][C:19]([C:25]3[CH:26]=[CH:27][C:28]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=4)=[CH:29][CH:30]=3)([CH2:10][O:9][C:7]3[NH:8][C:4]4[CH:3]=[C:2]([Cl:1])[C:40]([Cl:41])=[CH:39][C:5]=4[N:6]=3)[CH2:20][CH2:21]2)[CH2:44][CH2:43]1

Participants

8

Reactant 4

HCID 123114CyclopropanecarboxaldehydeHCID 2724141Tetrabutylammonium FluorideHCID 5049666Sodium triacetoxyborohydrideHCID 67218842HCID 67218842, compound

Product 1

HCID 11283992HCID 11283992, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.045 g of 4′-{4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidin-4-yl}-biphenyl-3-carbonitrile 55 (0.073 mmol, 1 eq) in 0.5 mL of 1,2-dichloroethane at room temperature was added 6.6 μL of cyclopropanecarboxaldehyde (0.088 mmol, 1.2 eq) and acetic acid (0.005 mL, 1% v/v). The mixture was stirred at room temperature for 1 h followed by the addition of 0.023 g of NaBH(OAc)3 (0.105 mmol, 1.5 eq). The reaction was stirred at room temperature for 16 h and then the solvent was removed by rotary evaporation to yield 0.052 g of the crude product. This intermediate was dissolved in 2 mL of tetrahydrofuran and tetrabutylammonium fluoride on silica gel (1.0-1.5 mmol/g, 0.16 g, 2 eq) was added. The mixture was heated to 60° C. for 16 h then filtered and the resin washed with 10 mL of tetrahydrofuran. The filtrate was concentrated by rotary evaporation and the crude product was purified by flash silica gel chromatography eluting with 1% methanol in dichloromethane with 3% triethylamine to give 0.007 g of the desired product 4′-[1-cyclopropylmethyl-4-(5,6-dichloro-1H-benzoimidazol-2-yloxymethyl)-piperidin-4-yl]-biphenyl-3-carbonitrile 57 MS (ESI): Calcd m/z for C30H28Cl2N4O.H+=531.2. Found m/z 530.9/532.9 [(M+1)+/(M+3)+].

Workup

  1. stirringThe reaction was stirred at room temperature for 16 h
  2. customthe solvent was removed by rotary evaporation
  3. customto yield 0.052 g of the crude product
  4. temperatureThe mixture was heated to 60° C. for 16 h
  5. filtrationthen filtered
  6. washthe resin washed with 10 mL of tetrahydrofuran
  7. concentrationThe filtrate was concentrated by rotary evaporation
  8. customthe crude product was purified by flash silica gel chromatography
  9. washeluting with 1% methanol in dichloromethane with 3% triethylamine

Sources & evidence

ORD record
ord-964e54fb5eef4dc182fd8e148150cfcc
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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