Triethylamine → (5R)-5-methyl-3-(4-{[2-methyl-5-(methyloxy)phenyl]oxy}phenyl)-2,4-imidazolidinedione

HRID 1505401Notes

Reaction equation

HRID 1505401 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[O:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:22])[C@@H:19]([CH3:21])[NH2:20])=[CH:13][CH:12]=1.C(N(CC)CC)C.Cl[C:31](Cl)([O:33]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>ClCCl>[CH3:21][C@H:19]1[NH:20][C:31](=[O:33])[N:17]([C:14]2[CH:15]=[CH:16][C:11]([O:10][C:3]3[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=3[CH3:1])=[CH:12][CH:13]=2)[C:18]1=[O:22]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 67235021N1-(4-{[2-methyl-5-(methyloxy)phenyl]oxy}phenyl)-D-alaninamide2×

Product 1

HCID 53241612(5R)-5-methyl-3-(4-{[2-methyl-5-(methyloxy)phenyl]oxy}phenyl)-2,4-imidazolidinedione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

N1-(4-{[2-methyl-5-(methyloxy)phenyl]oxy}phenyl)-D-alaninamide (Intermediate 16, 118 mg) was dissolved in dry dichloromethane (18 mL). The reaction mixture was cooled down in an ice bath. Triethylamine 0.327 mL, 2.350 mmol) was added. Then a solution of triphosgene in dry dichloromethane (46.5 mg, 0.157 mmol) dissolved in 7 mL of dichloromethane was added. The reaction was stirred at 0° C. for 10 min under argon. A saturated aqueous solution of NaHCO3 was added (18 mL) and the aqueous layer was extracted with dichloromethane 4 times (4×15 mL). After drying over sodium sulphate, the solvents were removed under vacuum. The residue was purified by silica gel chromatography (Companion system, 12 g cartridge) eluting with a gradient cHex/EOAc from to 100/0 to 60/40 during 20 min and 60/40 during 30 min. This afforded the title compound (91 mg).

Workup

  1. temperatureThe reaction mixture was cooled down in an ice bath
  2. additionwas added
  3. extractionthe aqueous layer was extracted with dichloromethane 4 times (4×15 mL)
  4. dry with materialAfter drying over sodium sulphate
  5. customthe solvents were removed under vacuum
  6. customThe residue was purified by silica gel chromatography (Companion system, 12 g cartridge)
  7. washeluting with a gradient cHex/EOAc from to 100/0 to 60/40 during 20 min
  8. wait60/40 during 30 min

Sources & evidence

ORD record
ord-d3f1f37f18a4472f942f824f48d547cd
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

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