Triethylamine → (2-{4-[4-(2-Carbamoylethyl)-phenoxy]-phenyl}-1-dimethylcarbamoylethyl)-carbamic acid tert-butyl ester

HRID 748983Notes

Reaction equation

HRID 748983 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:29](=[O:33])[N:30]([CH3:32])[CH3:31])[CH2:10][C:11]1[CH:28]=[CH:27][C:14]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([OH:26])=O)=[CH:18][CH:17]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:36](CC)CC)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:29](=[O:33])[N:30]([CH3:32])[CH3:31])[CH2:10][C:11]1[CH:28]=[CH:27][C:14]([O:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:22][CH2:23][C:24](=[O:26])[NH2:36])=[CH:20][CH:21]=2)=[CH:13][CH:12]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 597628113-{4-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-phenyl}-propionic acid

Product 1

HCID 59762815(2-{4-[4-(2-Carbamoylethyl)-phenoxy]-phenyl}-1-dimethylcarbamoylethyl)-carbamic acid tert-butyl esterYield 99.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acid compound 6 (1.5 g, 3.3 mmol) was dissolved in DCM (25 mL). Triethylamine (0.55 mL, 3.94 mmol) and BOP reagent (1.6 g, 3.61 mmol) were added and the reaction mixture stirred at room temperature for 15 min under an atmosphere of argon. Ammonia gas was then bubbled gently through the solution for 15-20 min to complete the reaction. Excess ammonia was degassed, the solvent was removed under reduced pressure and the residue was suspended in EtOAc (75 mL). The organic layer was washed with 0.5 N NaOH (2×10 mL), water (2×25 mL), and brine (1×30 mL), dried and concentrated under reduced pressure to yield the amide compound 11 (1.5 g, ˜99%). 1H NMR (DMSO-d6): 7.27 (br, 1H), 7.25 (d, J=8.4 Hz, 2H), 7.19 (d, J=8.4 Hz, 2H), 7.06 (d, J=8.4 Hz, 1H), 6.88 (d, J=8.8 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 6.75 (br, 1H), 4.53 (m, 1H), 2.91 (s, 3H), 2.75-2.83 (m, 7H), 2.33 (t, J=7.6 Hz, 2H), 1.32 (s, 9H)

Workup

  1. customAmmonia gas was then bubbled gently through the solution for 15-20 min
  2. customthe reaction
  3. customExcess ammonia was degassed
  4. customthe solvent was removed under reduced pressure
  5. washThe organic layer was washed with 0.5 N NaOH (2×10 mL), water (2×25 mL), and brine (1×30 mL)
  6. customdried
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-32b89edd02b2461380e9ef94f21079f3
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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