Water → tert-Butyl 4-((1-(6-chloro-1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913942Notes

Reaction equation

HRID 913942 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]([O:23][CH2:24][C:25]2([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]2)[CH3:22])[C:5]2[N:9](COCC[Si](C)(C)C)[C:8](=[O:18])[N:7]([CH3:19])[C:6]=2[CH:20]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]([O:23][CH2:24][C:25]2([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH2:29][CH2:30]2)[CH3:22])[C:5]2[NH:9][C:8](=[O:18])[N:7]([CH3:19])[C:6]=2[CH:20]=1

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 57546159tert-Butyl 4-((1-(6-chloro-1-methyl-2-oxo-3-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 57546176tert-Butyl 4-((1-(6-chloro-1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl 4-((1-(6-chloro-1-methyl-2-oxo-3-((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (53 mg, 0.082 mmol) was dissolved in tetrabutylammonium fluoride (1M in tetrahydrofuran, 1 mL, 1 mmol) and immersed in an oil bath which was pre-heated to 60° C. After 1.5 h, the temperature was increased to 65° C. and stirred at that temperature for 5 h. The reaction was sealed and heated at 70° C. overnight. The crude reaction mixture was diluted with diethyl ether and poured into water. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate and concentrated. Column chromatography (25%→75% ethyl acetate/n-hexane) gave 26 mg (61%) as a colorless film. 1H-NMR (CDCl3, 500 MHz) δ 7.66 (bs, 1H), 7.25 (dd, J=8.6, 5.5 Hz, 2H), 7.05 (dd, J=8.9, 8.6 Hz, 2H), 6.80 (d, J=1.5 Hz, 1H), 6.66 (d, J=1.8 Hz, 1H), 4.29 (q, J=6.7 Hz, 1H), 3.73 (m, 2H), 3.32 (d, J=9.2 Hz, 1H), 3.31 (s, 3H), 3.27 (d, J=9.2 Hz, 1H), 2.87-3.12 (m, 2H), 2.20 (m, 1H), 2.06 (m, 1H), 1.81 (m, 1H), 1.74 (bs, 1H), 1.43 (s, 9H), 1.32 (d, J=6.4 Hz, 3H). Mass spec.: 540.10 (MNa)+.

Workup

  1. customimmersed in an oil bath
  2. temperaturethe temperature was increased to 65° C.
  3. customThe reaction was sealed
  4. temperatureheated at 70° C. overnight
  5. customThe crude reaction mixture
  6. washThe ethereal was washed with water (2×)
  7. dry with materialbrine, dried over magnesium sulfate
  8. concentrationconcentrated
  9. customColumn chromatography (25%→75% ethyl acetate/n-hexane) gave 26 mg (61%) as a colorless film

Sources & evidence

ORD record
ord-dc3fe1dfdc104eda9d258d7f3911edec
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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