Toluene → 4-(Dimethylamino)pyridine

HRID 1653932Notes

Reaction equation

HRID 1653932 reaction equation
[C:1]1(C)[CH:6]=[CH:5]C=[CH:3][CH:2]=1.[CH3:8][N:9]1[CH2:14]COCC1.[NH2:15][C@H](C(NC1C=CC=CC=1)=O)CC(C)C>CN(C=O)C.CCOC(C)=O>[CH3:8][N:9]([CH3:14])[C:1]1[CH:6]=[CH:5][N:15]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 1140TolueneHCID 79724-MethylmorpholineHCID 11031002L-leucine anilide

Product 1

HCID 142844-(Dimethylamino)pyridineYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The crude carboxylic acid (45 mg, 0.11 mmol) was dried by evaporation of a toluene solution and then dissolved in DMF (0.40 mL). Molecular sieves (4 Å, 0.16 g) and N-methylmorpholine (0.027 mL, 25 mg, 0.25 mmol) were added. After 10 min., benzotfiazol-1-yloxytris(dimethylamino)phosphonium hexafiuorophosphate (60 mg, 0.14 mmol) was added and the solution was stirred for 40 min. before the addition of L-leucine anilide (28 mg, 0.14 mmol). After 1.5 h at room temperature, the solution was diluted with 20 mL of EtOAc and washed with 2 N aq. HCl (10 mL), saturated aq. NaHCO3 (10 mL), and saturated aq. NaCl (10 mL). The organic layer was dried (Na2SO4), decanted, and evaporated. Purification by flash column chromatography on silica gel (4.7 g) eluting with 100 mL of 3% EtOAc/dichloromethane gave 55 mg (83% yield) of the title compound as a colorless film. NMR (400 MHz, CDCl3) indicated a 1:1 mixture of diastereomers: δ8.50 (s, 1 H), 7.47 (d, 2H, J=7 Hz), 7.38-7.29 (m, 5H), 7.25 (t, 2H, J=7 Hz), 7.06 (t, 1H, J=7 Hz), 7.04 (d, 1H, J=8 Hz), 7.02 (d, 1H, J=8 Hz), 6.96 (d, 1H, J=8 Hz), 6.93 (d, 1H, J=8 Hz), 6.21 (d, 0.5H, J=8 Hz), 6.16 (d, 0.5H, J=8 Hz), 5.11 (s, 2H), 4.66 (bq, 1H, J=7 Hz), 2.95 (quintet, 0.5 H, J=8 Hz), 2.92 (quintet, 0.5H, J=8 Hz), 2.60-2.37 (m, 5H), 2.16-2.06 (m, 1H), 2.00-1.54 (m, 11H), 0.99 (d, 3H, J=6 Hz), 0.97 (d, 1.5H, J=6 Hz), 0.96 (d, 1.5 H, J=6 Hz), 0.93 (t, 1.5H, J=7 Hz), 0.92 (t, 1.5H, J=7 Hz).

Workup

  1. waitAfter 1.5 h at room temperature
  2. washwashed with 2 N aq. HCl (10 mL), saturated aq. NaHCO3 (10 mL), and saturated aq. NaCl (10 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. customdecanted
  5. customevaporated
  6. customPurification by flash column chromatography on silica gel (4.7 g)
  7. washeluting with 100 mL of 3% EtOAc/dichloromethane

Sources & evidence

ORD record
ord-59302b0d5e784895a91b9b5df86d7e00
Source dataset
uspto-grants-1995_04
Patent number
US05403952

Reaction notes

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