2-Methoxyphenylacetic acid → N-heptyl-2-(2-methoxyphenyl)acetamide

HRID 2112040Notes

Reaction equation

HRID 2112040 reaction equation
[CH2:1]([NH2:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH3:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][C:18](O)=[O:19].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C.CCOC(C)=O>[CH2:1]([NH:8][C:18](=[O:19])[CH2:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[O:10][CH3:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]

Participants

7

Reactant 4

HCID 71342-Methoxyphenylacetic acidHCID 81271-HeptanamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 3375995N-heptyl-2-(2-methoxyphenyl)acetamideYield 87.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Heptan-1-amine (1 g, 8.679 mmol was dissolved in DMF (10 ml), (2-methoxyphenyl)acetic acid (1.587 g, 9.547 mmol) was added and the mixture was cooled to 0° C. N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (3.065, 9.547 mmol) and N-ethyl-N,N-diisopropylamine (2.356 g, 18.226 mmol) were added. The solution was stirred overnight at room temperature. EtOAc (20 ml) was added and the organic phase was washed with two portions of NaHCO3 (2×20 ml, aq). The organic layer was dried (MgSO4) and the solvent was removed by evaporation. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation to give 2.00 g of N-heptyl-2-(2-methoxyphenyl)acetamide (yield 87.5%).

Workup

  1. washthe organic phase was washed with two portions of NaHCO3 (2×20 ml, aq)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe solvent was removed by evaporation
  4. customThe crude was purified by preparative HPLC (
  5. concentrationthe acetonitrile concentration
  6. temperaturewas increased to 100%
  7. additiona mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min)
  8. additionThe product containing fractions
  9. customthe acetonitrile was removed by evaporation EtOAc (10 ml)
  10. additionwas added
  11. washthe organic phase was washed with two portions of brine
  12. dry with materialdried (MgSO4)
  13. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-ac1fe9d7f8f843638cb2d91c81943f64
Source dataset
uspto-grants-2009_04
Patent number
US07521461B2

Reaction notes

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