Triethylamine → tert-Butyl 2-(6-chloronicotinamido)phenylcarbamate

HRID 1805284Notes

Reaction equation

HRID 1805284 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH2:14])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][N:25]=1>CC#N>[Cl:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH:14][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[NH:7][C:6](=[O:15])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:29])=[CH:26][N:25]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 792226-Chloronicotinic acidHCID 676311N-(tert-Butoxycarbonyl)-1,2-phenylenediamine

Product 1

HCID 57717462tert-Butyl 2-(6-chloronicotinamido)phenylcarbamateYield 92%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To solution of (2-amino-phenyl)-carbamic acid tert-butyl ester (22) (Seto, C. T.; Mathias, J. P.; Whitesides, G. M.; J. Amer. Chem. Soc., (1993), 115, 1321-1329.) (1.56 g, 7.49 mmol) in MeCN (40 mL) is added triethylamine (2.60 mL, 18.7 mmol) and 6-chloronicotinic acid (1.42 g 8.99 mmol). The mixture is stirred for 18 h at r.t. Upon completion of the reaction, the solvent is removed in vacuo and the residue is partitioned between EtOAc and an NH4Cl solution. The organic phase is collected and the aqueous layer is then extracted with EtOAc; the combined organic layers are washed with brine, dried over MgSO4 and evaporated. The residue is purified by flash chromatography using EtOAc/Hexane (a gradient of 20:80 to 50:50) as an eluent, to afford the title compound 94 (2.39 g, 92% yield). 1H NMR (DMSO-d6) δ(ppm): 10.01 (s, 1H), 8.96 (d, J=2.0 Hz, 1H), 8.71 (s, 1H), 8.35 (dd, J=8.4, 2.4 Hz, 1H), 7.73 (d, J=8.0 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.48 (d, J=7.6 Hz, 1H), 7.22 (td, J=7.8, 1.4 Hz, 1H), 7.13 (t, J=7.6 Hz, 1H), 1.44 (s, 9H). LRMS (ESI): (calc) 347.10 (found) 370.1 (M+Na+).

Workup

  1. customUpon completion of the reaction
  2. customthe solvent is removed in vacuo
  3. customthe residue is partitioned between EtOAc
  4. customThe organic phase is collected
  5. extractionthe aqueous layer is then extracted with EtOAc
  6. washthe combined organic layers are washed with brine
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe residue is purified by flash chromatography

Sources & evidence

ORD record
ord-a9aba65ecf4341d682b831860b10ce5b
Source dataset
uspto-grants-2013_01
Patent number
US08354445B2

Reaction notes

Loading…