Tetrabutylammonium Fluoride → HCID 11387347, compound

HRID 1788285Notes

Reaction equation

HRID 1788285 reaction equation
[Cl:1][C:2]1[C:44]([Cl:45])=[CH:43][C:5]2[NH:6][C:7]([O:9][CH:10]([C:19]3([C:29]4[CH:34]=[CH:33][C:32]([C:35]5[CH:40]=[CH:39][CH:38]=[C:37]([C:41]#[N:42])[CH:36]=5)=[CH:31][CH:30]=4)[CH2:24][CH2:23][N:22]([S:25]([CH3:28])(=[O:27])=[O:26])[CH2:21][CH2:20]3)COCC[Si](C)(C)C)=[N:8][C:4]=2[CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:44]([Cl:45])=[CH:43][C:5]2[NH:6][C:7]([O:9][CH2:10][C:19]3([C:29]4[CH:30]=[CH:31][C:32]([C:35]5[CH:40]=[CH:39][CH:38]=[C:37]([C:41]#[N:42])[CH:36]=5)=[CH:33][CH:34]=4)[CH2:20][CH2:21][N:22]([S:25]([CH3:28])(=[O:26])=[O:27])[CH2:23][CH2:24]3)=[N:8][C:4]=2[CH:3]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67219167HCID 67219167, compound

Product 1

HCID 11387347HCID 11387347, compoundYield 44.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 0.044 g of crude 4′-{4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-1-methanesulfonyl-piperidin-4-yl}-biphenyl-3-carbonitrile from the previous step (˜0.05 mmol) in 2 mL of tetrahydrofuran was added tetrabutylammonium fluoride (1M in THF, 0.1 mL, 0.1 mmol, 2 eq) and the resulting mixture was heated to 60° C. for 18 h. After cooling to room temperature, the reaction mixture was diluted with 10 mL of ethyl acetate and washed with H2O and saturated brine. The organic extracts were combined and dried over Na2SO4, filtered and concentrated by rotary evaporation to give the crude product as a pale foam. Purification by flash silica gel chromatography eluting with a gradient of 20-70% ethyl acetate in hexane gave a pale foam which was re-purified by reverse phase preparative HPLC to yield 0.016 g of the desired product 4′-[4-(5,6-dichloro-1H-benzoimidazol-2-yloxymethyl)-1-methanesulfonyl-piperidin-4-yl]-biphenyl-3-carbonitrile 56 as a white foam. 1H NMR (300 MHz, CDCl3): δ 7.84-7.83 (t, 1H), 7.80-7.77 (dt, 1H), 7.66-7.44 (m, 8H), 4.54 (s, 2H), 3.64-3.40 (d, 2H), 3.02-2.95 (t, 2H), 2.74 (s, 3H), 2.60 (br. s, 1H), 2.47-2.43 (d, 2H), 2.22-2.12 (t, 2H). MS (ESI): Calcd m/z for C27H24Cl2N4O3S.H+=554.1. Found m/z=554.6/556.7 [(M+1)+/(M+3)+].

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with H2O and saturated brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customto give the crude product as a pale foam
  7. customPurification by flash silica gel chromatography
  8. washeluting with a gradient of 20-70% ethyl acetate in hexane
  9. customgave a pale foam which
  10. customwas re-purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-fb978749489047c8a4be6a0bfb025eb6
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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