Hydrochloric Acid → 3-Benzyl-3-methyl-2,3-dihydro-benzofuran-6-carboxylic acid (2-iodo-phenyl)-amide

HRID 523504Notes

Reaction equation

HRID 523504 reaction equation
[CH2:1]([C:8]1([CH3:20])[C:12]2[CH:13]=[CH:14][C:15]([C:17]([OH:19])=O)=[CH:16][C:11]=2[O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I:21][C:22]1[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=1[NH2:24].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl>ClCCl.CN(C=O)C>[I:21][C:22]1[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=1[NH:24][C:17]([C:15]1[CH:14]=[CH:13][C:12]2[C:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)([CH3:20])[CH2:9][O:10][C:11]=2[CH:16]=1)=[O:19]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 119952-IodoanilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251290473-Benzyl-3-methyl-2,3-dihydro-benzofuran-6-carboxylic acid

Product 1

HCID 594431273-Benzyl-3-methyl-2,3-dihydro-benzofuran-6-carboxylic acid (2-iodo-phenyl)-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of 3-Benzyl-3-methyl-2,3-dihydro-benzofuran-6-carboxylic acid (80 mg, 0.3 mmol) and 2-Iodoaniline (72 mg, 0.33 mmol) in dichloromethane (3 mL) and DMF (2 mL) were added O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (125 mg, 0.33 mmol) and then a solution of N,N-diisopropylethylamine (58 mg, 78 μL, 0.45 mmol, mL) in DMF (1 mL). The reaction mixture was stirred at ambient temperature for 18 h. The reaction medium is acidified by adding a 1.2 M hydrochloric acid solution and extracted with ethyl acetate. The organic phase is washed with water, dried (MgSO4), and concentrated to give the amide which is purified by flash chromatography (AcOEt/heptane: 4/6). The column was chosen too small and a bigger column was chosen (AcOEt/heptane: 4/6) to afford 22 mg of the desired amid as a pale yellow solid (16%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase is washed with water
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-169aea11980949a3904d35605d7839de
Source dataset
uspto-grants-2016_05
Patent number
US09339486B2

Reaction notes

Loading…