Pyridine → Methyl (S)-4,4-difluoro-2-isocyanato-5-phenylpentanoate

HRID 1664733Notes

Reaction equation

HRID 1664733 reaction equation
[NH2:1][C@@H:2]([CH2:7][C:8]([F:17])([F:16])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:3]([O:5][CH3:6])=[O:4].N1C=CC=CC=1.[C:24](Cl)(Cl)=[O:25]>ClCCl.C1(C)C=CC=CC=1>[F:17][C:8]([F:16])([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:7][C@H:2]([N:1]=[C:24]=[O:25])[C:3]([O:5][CH3:6])=[O:4]

Participants

6

Reactant 3

HCID 1049PyridineHCID 6371PhosgeneHCID 59430997Methyl (S)-2-amino-4,4-difluoro-5-phenylpentanoate

Product 1

HCID 86635603Methyl (S)-4,4-difluoro-2-isocyanato-5-phenylpentanoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

817 mg of methyl (S)-2-amino-4,4-difluoro-5-phenylpentanoate (3.36 mmol) were dissolved in 20 ml of dichloromethane, admixed with 1.08 ml of pyridine (4 eq.) and cooled to approx. 5° C. (ice bath). After 10 min, 2.3 ml (1.3 eq.) of a 20% phosgene solution in toluene were added dropwise. The resulting suspension was stirred with ice bath cooling for 4 h and then concentrated under reduced pressure. The residue thus obtained was taken up in toluene and filtered. After the solvent had been removed under reduced pressure, methyl (S)-4,4-difluoro-2-isocyanato-5-phenylpentanoate was obtained as an orange oil which was used without further purification in the subsequent reaction. Yield: 943 mg (quant.)

Workup

  1. temperaturecooling for 4 h
  2. concentrationconcentrated under reduced pressure
  3. customThe residue thus obtained
  4. filtrationfiltered
  5. customAfter the solvent had been removed under reduced pressure

Sources & evidence

ORD record
ord-3a5ae92f175f4ffea617db13cda52c54
Source dataset
uspto-grants-2011_10
Patent number
US08039480B2

Reaction notes

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