Diisopropylethylamine → 4-fluoro-2-hydroxy-N-(3-nitro-benzyl)-benzamide

HRID 457952

Reaction equation

HRID 457952 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:11])[C:5](=[CH:9][CH:10]=1)[C:6](Cl)=[O:7].C(N(CC)C(C)C)(C)C.Cl.[N+:22]([C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH2:28][NH2:29])([O-:24])=[O:23]>ClCCl>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:29][CH2:28][C:27]2[CH:30]=[CH:31][CH:32]=[C:25]([N+:22]([O-:24])=[O:23])[CH:26]=2)=[O:7])=[C:4]([OH:11])[CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2724030Benzenemethanamine, 3-nitro-, hydrochloride (1:1)HCID 184681274-Fluoro-2-hydroxybenzoyl chloride

Product 1

HCID 184681804-fluoro-2-hydroxy-N-(3-nitro-benzyl)-benzamideYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-fluoro salicylic acid chloride (12.3 g, 70.3 mmol) in dichloromethane (140 mL) was cooled to 0° C., and treated with N,N-diisopropylethylamine (31.0 mL, 175 mmol) and 3-nitrobenzylamine hydrochloride (16 g, 84.6 mmol). After stirring at room temperature for 24 h, the solution was concentrated in vacuo and diluted with ethyl acetate. The organic layer was washed successively with aq 2 N HCl and saturated aq NaCl, dried over MgSO4, filtered and concentrated. Purification by MPLC (10–100% ethyl acetate in heptane, 23 mL/min, 75 min) provided 4-fluoro-2-hydroxy-N-(3-nitro-benzyl)-benzamide as a yellow solid (13.7 g, 67%): 1H NMR (DMSO-d6 300 MHz) δ 12.75 (s, 1 H), 9.43 (t, J=6.0 Hz, 1 H), 8.11 (ddd, J, =8.3, J2=2.1 Hz, J3=1.2 Hz, 1 H), 8.18 (t, J=1.5 Hz, 1 H), 7.94 (dd, J1=8.9 Hz, J2=6.5 Hz, 1 H), 7.78 (td, J1=7.8 Hz, J2=1.4 Hz, 1 H), 7.63 (t, J=8.0 Hz, 1 H), 6.81–6.72 (m, 2 H), 4.61 (d, J=5.7 Hz, 2 H).

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. washThe organic layer was washed successively with aq 2 N HCl and saturated aq NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by MPLC (10–100% ethyl acetate in heptane, 23 mL/min, 75 min)

Sources & evidence

ORD record
ord-38414f88160f43a6a8c3b49f271ca38b
Source dataset
uspto-grants-2007_03
Patent number
US07189749B2

Linked notes

Loading…