Dimethylamine → 3-{4-[4-(Tert-butoxycarbonylaminodimethylcarbamoylmethyl)-phenoxy]-phenyl}-propionic acid methyl ester

HRID 749003Notes

Reaction equation

HRID 749003 reaction equation
[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:20]([OH:22])=O)=[CH:15][CH:14]=2)=[CH:8][CH:7]=1.[CH2:32]([N:34](CC)[CH2:35]C)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CNC>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]([O:12][C:13]2[CH:14]=[CH:15][C:16]([CH:19]([NH:23][C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[C:20](=[O:22])[N:34]([CH3:35])[CH3:32])=[CH:17][CH:18]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 597511053-{4-[4-(Tert-butoxycarbonylaminocarboxymethyl)-phenoxy]-phenyl}-propionic acid methyl ester

Product 1

HCID 597511213-{4-[4-(Tert-butoxycarbonylaminodimethylcarbamoylmethyl)-phenoxy]-phenyl}-propionic acid methyl esterYield 87.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The hydrogenated compound 31 (4.0 g, 9.3 mmol) was dissolved in CH2Cl2 (60 mL) and stirred at room temperature under an atmosphere of argon. Triethylamine (1.56 mL, 11.0 mmol) and BOP reagent (4.53 g, 10.0 mmol) were added and the reaction mixture was stirred for 15 min. Dimethylamine (2.0 M solution in THF, 23.3 mL, 47.0 mmol) was added and the resulting solution was stirred at room temp for about 2-3 h. The solvent was removed under reduced pressure and the resulting oil was taken up in EtOAc (200 mL). The organic layer was extracted with 0.5 N NaOH (1×30 mL), water (2×100 mL) and brine (1×100 mL). Drying and concentration of the organic layer gave the desired amide 32 (3.7 g, 87%). 1H NMR (400 MHz, DMSO-d6): 7.34 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.0 Hz, 2H), 6.93 (overlapped d, J=8.8 Hz, 2H), 6.92 (overlapped d, J=8.0 Hz, 2H), 5.50 (d, J=8.0 Hz, 1H), 3.59 (s, 3H), 2.90 (s, 3H), 2.80-2.84 (m. 5H), 2.63 (t, J=7.6 Hz, 2H), 1.37 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 15 min
  2. stirringthe resulting solution was stirred at room temp for about 2-3 h
  3. customThe solvent was removed under reduced pressure
  4. extractionThe organic layer was extracted with 0.5 N NaOH (1×30 mL), water (2×100 mL) and brine (1×100 mL)
  5. customDrying

Sources & evidence

ORD record
ord-81c65d5bb2f64f0c987ff6df401beb54
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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