Dimethylformamide → Benzamide

HRID 1533482Notes

Reaction equation

HRID 1533482 reaction equation
ON1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2N=N1.C(N=C=NC(C)C)(C)C.C[N:21](C)[CH:22]=[O:23]>>[C:22]([NH2:21])(=[O:23])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 757711-Hydroxybenzotriazole

Product 1

HCID 2331BenzamideYield 98%

Procedure

Rink amide resin (1.786 g; 1.00 mmol) is deprotected as described previously. The deprotected resin is shaken in a solution prepared from 4d (745 mg; 2.00 mmol), 1-hydroxybenzotriazole (810 mg, 6.00 mmol), N,N′-diisopropyl carbodiimide (1.010 g, 8.00 mmol) and dimethylformamide (100 mL) overnight at room temperature. The resin is washed thoroughly with several portions of dimethylformamide, then methanol, and finally dichloromethane. The washing continues until the latest filtrate is free of fluorescence. Solvents are evaporated under reduced pressure at room temperature. An aliquot of product (7a) is cleaved from the solid support (200 mg) by treatment of the resin with a 2:1 mixture of dichloromethane and triluoroacetic acid (10 mL) for 10 min. The solution is collected by vacuum filtration. The resin is further extracted with three portions of dichloromethane, followed by two portions of dimethylformamide. Removal of the solvents under reduced pressure and drying overnight in a desiccator provides 34.0 mg (98%) of 7a: mp 267-269° C.; homogeneous by thin layer chromatography: Rf=0.68; dichloromethane: methanol=9:1); 1H-NMR (DMSO-d6): 3.92 (s, 3H, OCH3); 7.43 (ddd, 1H); 7.61 (ddd, 1H); 7.95-8.00 (m, 3H); 8.13-8.16 (m, 4H); 8.23-8.25 (m, 3H); CONH2 broad (not assignable); 13C-NMR (DMSO-d6): 51.9 (COOCH3); 121.2; 121.6; 122.6; 123.0; 127.3; 127.9; 129.0; 129.4; 129.7; 132.5; 136.8; 139.9; 141.4; 144.4; 165.9 (CONH2); 167.03 (COOCH3).

Workup

  1. washThe resin is washed thoroughly with several portions of dimethylformamide
  2. customSolvents are evaporated under reduced pressure at room temperature
  3. additionAn aliquot of product (7a) is cleaved from the solid support (200 mg) by treatment of the resin with a 2:1 mixture of dichloromethane and triluoroacetic acid (10 mL) for 10 min
  4. filtrationThe solution is collected by vacuum filtration
  5. extractionThe resin is further extracted with three portions of dichloromethane
  6. customRemoval of the solvents under reduced pressure
  7. customdrying overnight in a desiccator

Sources & evidence

ORD record
ord-dddf9e37928c48deb005e8df11f6e07c
Source dataset
uspto-grants-2001_03
Patent number
US06207831B1

Reaction notes

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