D-Alanine → HCID 68322495, compound

HRID 1505306Notes

Reaction equation

HRID 1505306 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:9][C:10]2[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].Cl[C:18](Cl)([O:20]C(=O)OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[NH2:38][C@@H:39]([C:41]([OH:43])=[O:42])[CH3:40]>ClCCl.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([O:9][C:10]2[CH:16]=[CH:15][C:13]([NH:14][C:18]([NH:38][C@@H:39]([C:41]([OH:43])=[O:42])[CH3:40])=[O:20])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 71080D-AlanineHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 26189737HCID 26189737, compound2×

Product 1

HCID 68322495HCID 68322495, compoundYield 302.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-[(3-chloro-4-fluorophenyl)oxy]aniline (Intermediate 8, 237 mg) and triphosgene (99 mg, 0.33 mmol) in 15 mL of dichloromethane was added DIPEA (155 mg, 1.2 mmol) and the mixture was stirred at room temperature for 2 hours. Then the solvent was evaporated to give a residue. The residue was dissolved in 5 mL of THF and was transferred to a mixture of DIPEA (65 mg, 0.5 mmol, Acros) and D-Alanine (89 mg, 1 mmol) in 5 mL of THF. The whole reaction mixture was stirred at room temperature for 16 hours. Removal of the solvent afforded the title compound (352 mg) which was directly used in the next step.

Workup

  1. customThen the solvent was evaporated
  2. customto give a residue
  3. customThe whole reaction mixture
  4. stirringwas stirred at room temperature for 16 hours
  5. customRemoval of the solvent

Sources & evidence

ORD record
ord-0539bdca6ddb442382f73e553bf93709
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

Loading…