Morpholine → 3-{4-[4-(2-Tert-butoxycarbonylamino-3-morpholin-4-yl-3-oxo-propyl)-phenoxy]-phenyl}-propionic acid methyl ester

HRID 748985Notes

Reaction equation

HRID 748985 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[CH:23][CH:22]=2)=[CH:16][CH:15]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[NH:67]1[CH2:72][CH2:71][O:70][CH2:69][CH2:68]1>C(Cl)Cl>[CH3:32][O:31][C:29](=[O:30])[CH2:28][CH2:27][C:24]1[CH:25]=[CH:26][C:21]([O:20][C:17]2[CH:18]=[CH:19][C:14]([CH2:13][CH:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[C:10]([N:67]3[CH2:72][CH2:71][O:70][CH2:69][CH2:68]3)=[O:12])=[CH:15][CH:16]=2)=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 597628022-Tert-butoxycarbonylamino-3-{4-[4-(2-methoxycarbonyl-ethyl)-phenoxy]-phenyl}-propionic acid

Product 1

HCID 597628203-{4-[4-(2-Tert-butoxycarbonylamino-3-morpholin-4-yl-3-oxo-propyl)-phenoxy]-phenyl}-propionic acid methyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The compound 4 (2.0 g, 4.6 mmol) was dissolved in CH2Cl2 (25 mL) and stirred at room temperature under an atmosphere of argon. Triethylamine (0.94 mL, 6.76 mmol) and BOP reagent (2.19 g, 4.96 mmol) were added and the reaction mixture was stirred for 15 min. Morpholine (0.79 mL, 9.02 mmol) was added and the resulting solution was stirred at room temperature for about 1 h. The solvent was removed under reduced pressure and the resulting oil was taken up in EtOAc (60 mL). The organic layer was extracted with 1.0 N NaOH (1×10 mL), water (2×20 mL) and brine (1×20 mL). Drying and concentration of the organic layer gave the desired amide 13 (1.7 g, ˜74%). 1H NMR (400 MHz, DMSO-d6): 7.24 (d, J=8.8 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 6.90 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 4.56 (m, 1H), 3.58 (s, 3H), 3.24-3.54 (m, 8H), 2.74-2.87 (m, 4H), 2.62 (t, J=6.0 Hz, 2H), 1.32 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 15 min
  2. stirringthe resulting solution was stirred at room temperature for about 1 h
  3. customThe solvent was removed under reduced pressure
  4. extractionThe organic layer was extracted with 1.0 N NaOH (1×10 mL), water (2×20 mL) and brine (1×20 mL)
  5. customDrying

Sources & evidence

ORD record
ord-abf18beb9afc40ce82967314aa3264a2
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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