Tetrabutylammonium Fluoride → HCID 11157447, compound

HRID 1788282Notes

Reaction equation

HRID 1788282 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:35]2[CH:40]=[CH:39][C:38]([C:41]3[CH:46]=[CH:45][CH:44]=[C:43]([C:47]#[N:48])[CH:42]=3)=[CH:37][CH:36]=2)([CH:14]([O:23][C:24]2[NH:28][C:27]3[CH:29]=[C:30]([Cl:34])[C:31]([Cl:33])=[CH:32][C:26]=3[N:25]=2)COCC[Si](C)(C)C)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:35]2[CH:36]=[CH:37][C:38]([C:41]3[CH:46]=[CH:45][CH:44]=[C:43]([C:47]#[N:48])[CH:42]=3)=[CH:39][CH:40]=2)([CH2:14][O:23][C:24]2[NH:25][C:26]3[CH:32]=[C:31]([Cl:33])[C:30]([Cl:34])=[CH:29][C:27]=3[N:28]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67218888HCID 67218888, compound

Product 1

HCID 11157447HCID 11157447, compoundYield 52.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 0.081 g of 4-(3′-cyano-biphenyl-4-yl)-4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidine-1-carboxylic acid tert-butyl ester 52 (0.115 mmol) in 5 mL of tetrahydrofuran at room temperature was added 0.23 mL of a solution of TBAF (1M in THF, 0.23 mmol, 2 eq). The mixture was heated at 60° C. for 6 h. After cooling to room temperature, the mixture was partitioned between 15 mL of ethyl acetate and 15 mL of H2O. The organic layer was separated, washed with saturated brine, dried (Na2SO4), and concentrated by rotary evaporation to give the crude product as a pale foam (0.070 g) which was purified by flash column chromatography eluting with 30% ethyl acetate in hexanes to give 0.035 g of 4-(3′-cyano-biphenyl-4-yl)-4-(5,6-dichloro-1H-benzoimidazol-2-yloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester 53 as a pale foam and 0.024 g of recovered starting material. 1H NMR (300 MHz, CDCl3): δ 7.82-7.75 (m, 2H), 7.64-7.52 (dt, 1H), 7.61-7.46 (m, 5H), 7.26 (s, 1H), 4.51 (s, 2H), 3.85-3.83 (d, 2H), 3.18-3.10 (t, 2H), 2.32-2.28 (d, 2H), 2.04-1.98 (t, 2H), 1.42 (s, 9H). MS (ESI): Calcd m/z for C31H30Cl2N4O3.H+=577.2. Found m/z=576.7/578.7 [(M+1)+/(M+3)+].

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between 15 mL of ethyl acetate and 15 mL of H2O
  3. customThe organic layer was separated
  4. washwashed with saturated brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated by rotary evaporation
  7. customto give the crude product as a pale foam (0.070 g) which
  8. customwas purified by flash column chromatography
  9. washeluting with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-488c2532ff4e4cd5b0402a9995a20f8e
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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