Triethylamine → tert-butyl 4-(4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate

HRID 2378968Notes

Reaction equation

HRID 2378968 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:16]=2C(O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:27]([CH2:30]C)CC)C.P(N=[N+]=[N-])(OC1C=CC=CC=1)(OC1C=CC=CC=1)=[O:33]>C1(C)C=CC=CC=1>[F:24][C:20]1[C:16]2[NH:27][C:30](=[O:33])[N:14]([CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]3)[C:15]=2[CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 590063302-(1-(Tert-butoxycarbonyl)piperidin-4-ylamino)-6-fluorobenzoic acid

Product 1

HCID 59006349tert-butyl 4-(4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

2-(1-(tert-Butoxycarbonyl)piperidin-4-ylamino)-6-fluorobenzoic acid (1.081 g, 3.19 mmol) and triethylamine (0.534 ml, 3.83 mmol) were combined and suspended in toluene (20 mL). Diphenyl azidophosphate (0.826 ml, 3.83 mmol) was added to the mixture. Reaction stirred at room temperature for 35 minutes. The reaction was heated to 80° C. for 1 hour. Solvent was removed in vacuo. Silica gel chromatography eluting ethyl acetate-hexanes afforded the title compound as white solid in 97% yield. 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 9.64 (s, 1 H) 6.94-7.02 (m, 1 H) 6.91 (d, J=8.24 Hz, 1 H) 6.82 (t, J=9.15 Hz, 1 H) 4.42-4.54 (m, 1 H) 4.31 (d, J=10.07 Hz, 2 H) 2.86 (t, J=12.67 Hz, 2 H) 2.21-2.35 (m, 2 H) 1.78-1.87 (m, 2 H) 1.49 (s, 9 H).

Workup

  1. customReaction
  2. temperatureThe reaction was heated to 80° C. for 1 hour
  3. customSolvent was removed in vacuo
  4. washSilica gel chromatography eluting ethyl acetate-hexanes

Sources & evidence

ORD record
ord-ed0fa41e46e14e17b17b87e8bca51cbb
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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