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

HRID 749009Notes

Reaction equation

HRID 749009 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:28](=[O:32])[N:29]([CH3:31])[CH3:30])[C:10]1[CH:27]=[CH:26][C:13]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23](O)=[O:24])=[CH:17][CH:16]=2)=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:35](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:10]1[CH:11]=[CH:12][C:13]([O:14][C:15]2[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][C:23](=[O:24])[NH2:35])=[CH:19][CH:20]=2)=[CH:26][CH:27]=1)[C:28](=[O:32])[N:29]([CH3:30])[CH3:31])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 597511203-{4-[4-(Tert-butoxycarbonylaminodimethylcarbamoylmethyl)-phenoxy]-phenyl}-propionic acid

Product 1

HCID 59751109({4-[4-(2-Carbamoylethyl)phenoxy]-phenyl}-dimethylcarbamoylmethyl)-carbamic acid tert-butyl esterYield 100.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acid compound 33 (0.7 g, 1.58 mmol) was dissolved in DCM (25 mL). Triethylamine (0.26 mL, 1.89 mmol) and BOP reagent (0.77 g, 1.74 mmol) were added and the reaction mixture stirred at room temp 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 38 (0.7 g, quantitative yield). 1H NMR (400 MHz, DMSO-d6): 7.33 (d, J=8.4 Hz, 2H), 7.30 (br, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.12 (d, J=8.0 Hz, 1H), 6.93 (overlapped d, J=8.8 Hz, 2H0, 6.92 (overlapped d, J=8.8 Hz, 2H), 6.78 (br, 1H), 5.50 (d, J=8.0 Hz, 1H), 2.90 (s, 3H), 2.84 (s, 3H), 2.79 (t, J=8.0 Hz, 2H), 2.35 (t, J=8.0 Hz, 2H), 1.37 (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-419a07c73770416e944f1b8f0be5ca42
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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