Triphosgene → (2R,4S)-5-biphenyl-4-yl-4-isocyanato-2-methyl-pentanoic acid ethyl ester

HRID 881835Notes

Reaction equation

HRID 881835 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.[CH2:14]([O:16][C:17](=[O:36])[C@H:18]([CH3:35])[CH2:19][C@H:20]([NH2:34])[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:24][CH:23]=1)[CH3:15]>C(Cl)Cl>[CH2:14]([O:16][C:17](=[O:36])[C@H:18]([CH3:35])[CH2:19][C@H:20]([N:34]=[C:2]=[O:4])[CH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:26][CH:27]=1)[CH3:15]

Participants

4

Reactant 2

HCID 94429TriphosgeneHCID 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride2×

Product 1

HCID 86648207(2R,4S)-5-biphenyl-4-yl-4-isocyanato-2-methyl-pentanoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a vigorously stirred 1:1 mixture of methylene chloride/8% aqueous NaHCO3 (30 mL) at 0° C. is added triphosgene (114 mg, 0.384 mmol). After stirring the mixture at 0° C. for 5 minutes, (2R,4S)-4-amino-5-biphenyl-4-yl-2-methyl-pentanoic acid ethyl ester hydrochloride (Intermediate 29: 400 mg, 1.15 mmol) is added and stirring is continued for 15 minutes. The organic phase is separated and dried over sodium sulfate. The solvent is removed under reduced pressure to furnish (2R,4S)-5-biphenyl-4-yl-4-isocyanato-2-methyl-pentanoic acid ethyl ester.

Workup

  1. stirringAfter stirring the mixture at 0° C. for 5 minutes
  2. stirringstirring
  3. customThe organic phase is separated
  4. dry with materialdried over sodium sulfate
  5. customThe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-da0fd043eb8f4cffbfda06f374e89322
Source dataset
uspto-grants-2015_03
Patent number
US08993631B2

Reaction notes

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