Tetrabutylammonium Fluoride → HCID 11307291, compound

HRID 1788290Notes

Reaction equation

HRID 1788290 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)([O:14][CH2:15][C:16]2[N:20](COCC[Si](C)(C)C)[C:19]3[CH:29]=[C:30]([F:34])[C:31]([F:33])=[CH:32][C:18]=3[N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][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)([O:14][CH2:15][C:16]2[NH:17][C:18]3[CH:32]=[C:31]([F:33])[C:30]([F:34])=[CH:29][C:19]=3[N:20]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 67218981HCID 67218981, compound

Product 1

HCID 11307291HCID 11307291, compoundYield 91.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.033 g of 4-(3′-cyano-biphenyl-4-yl)-4-[5,6-difluoro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester 62 (0.05 mmol, 1 eq) in 2.5 mL of tetrahydrofuran was added 0.10 mL tetrabutylammonium fluoride (1M in THF, 0.1 mmol, 2 eq). The reaction was stirred at room temperature for 20 h and then at 60° C. for 5 h. The mixture was allowed to cool to room temperature and then partitioned between 25 mL of ethyl acetate and 20 mL of H2O. The organic layer was separated, washed with saturated brine, dried (Na2SO4), and concentrated to give the crude product which was purified by flash silica gel chromatography eluting with a gradient of 10-50% ethyl acetate in hexane to yield 0.025 g of the desired product 4-(3′-cyano-biphenyl-4-yl)-4-(5,6-difluoro-1H-benzoimidazol-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester 63 as a pale foam: 1H NMR (300 MHz, CDCl3): δ 9.96 (br. s., 1H), 7.82-7.81 (m, 1H), 7.78-7.75 (dt, 1H), 7.65-7.61 (m, 1H), 7.57-7.40 (m, 6H), 7.30-7.24 (m, 1H), 4.43 (s, 2H), 4.00 (d, 2H), 3.31-3.23 (t, 2H), 2.24-2.19 (d, 2H), 2.07-1.97 (td, 2H), 1.48 (s, 9H); MS (ESI): Calcd m/z for C31H30F2N4O3.H+=545.2. Found m/z=545 (M+1)+.

Workup

  1. waitat 60° C. for 5 h
  2. temperatureto cool to room temperature
  3. custompartitioned between 25 mL of ethyl acetate and 20 mL of H2O
  4. customThe organic layer was separated
  5. washwashed with saturated brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customto give the crude product which
  9. customwas purified by flash silica gel chromatography
  10. washeluting with a gradient of 10-50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-7a22537c5391467097cb0b6136ff66c5
Source dataset
uspto-grants-2009_03
Patent number
US07511146B2

Reaction notes

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