4-Formylbenzoic acid → Tert-butyl {2-[(4-formylbenzoyl)amino]phenyl}carbamate

HRID 1174603Notes

Reaction equation

HRID 1174603 reaction equation
[C:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1)([OH:3])=O.S(Cl)(Cl)=O.[C:16]([O:20][C:21](=[O:30])[NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[NH2:29])([CH3:19])([CH3:18])[CH3:17].C(C1C=CC(C(Cl)=O)=CC=1)=O.C(N(C(C)C)CC)(C)C>ClCCl.CN(C=O)C>[C:16]([O:20][C:21](=[O:30])[NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[NH:29][C:1](=[O:3])[C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1)([CH3:19])([CH3:17])[CH3:18]

Participants

8

Reactant 5

HCID 120884-Formylbenzoic acidHCID 24386Thionyl Chloride2×HCID 81531DiisopropylethylamineHCID 676311N-(tert-Butoxycarbonyl)-1,2-phenylenediamineHCID 124246204-Formylbenzoyl chloride

Product 1

HCID 22668143Tert-butyl {2-[(4-formylbenzoyl)amino]phenyl}carbamateYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

To a suspension of 4-carboxybenzaldehyde (6 g, 40 mmol) in dichloromethane (10 mL) was added thionyl chloride (4.1 mL, 56 mmol, 1.4 eq), followed by DMF (1 mL) dropwise. The mixture was refluxed for 4 hours and excess of thionyl chloride and DMF were removed under reduced pressure. To a solution of (2-aminophenyl)-carbamic acid tert-butyl ester (8.32 g, 40 mmol, 1 eq) in dichloromethane (80 mL), stirred at 0° C., was added a suspension of 4-formyl benzoyl chloride in dichloromethane (20 mL), followed by diisopropyl ethylamine (3.61 mL, 20 mmol, 1 eq). The mixture was stirred for 30 minutes at 0° C. then at room temperature for 30 minutes. The crude residue was diluted with dichloromethane (300 mL) and washed with water. The combined organic layers were dried (MgSO4), filtered and concentrated under vacuo. The crude residue was purified by column chromatography on silica gel (elution 20% ethyl acetate in hexane) to give 6.1 g (45% yield) of anilide 315. 1H NMR (CDCl3): δ 10.18 (s, 1H), 9.64 (brs, 1H), 8.20 (d, J=7.9 Hz 2H), 8.06 (d, J=7.9 Hz, 2H), 7.96 (d, J=7.9 Hz, 1H), 7.28-7.38 (m, 1H), 7.24 (d, J=4.4 Hz, 1H), 6.84 (s, 1H, 6.81 (d, J=8.8 Hz, 1H), 1.58 (s, 9H).

Workup

  1. customwere removed under reduced pressure
  2. additionwas added
  3. waitat room temperature for 30 minutes
  4. washwashed with water
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuo
  8. customThe crude residue was purified by column chromatography on silica gel (elution 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8683d4b6599c469e95ee93c96d5481a3
Source dataset
uspto-grants-2010_11
Patent number
US07838520B2

Reaction notes

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