Pyridine → Methyl (S)-4,4-difluoro-2-isocyanatopentanoate

HRID 1913335Notes

Reaction equation

HRID 1913335 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:8][C:9]([F:12])([F:11])[CH3:10])[C:4]([O:6][CH3:7])=[O:5].N1C=CC=CC=1.[C:19](Cl)(Cl)=[O:20]>ClCCl.C1(C)C=CC=CC=1>[F:12][C:9]([F:11])([CH3:10])[CH2:8][C@H:3]([N:2]=[C:19]=[O:20])[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 3

HCID 1049PyridineHCID 6371PhosgeneHCID 86635604methyl (S)-2-amino-4,4-difluoropentanoate hydrochloride

Product 1

HCID 57946243Methyl (S)-4,4-difluoro-2-isocyanatopentanoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

Under argon, 2.0 g of methyl (S)-2-amino-4,4-difluoropentanoate hydrochloride (9.8 mmol) were dissolved in 80 ml of dichloromethane, admixed with 3.2 ml of pyridine (4 eq.) and cooled to approx. 5° C. (ice bath). After 10 min, 6.7 ml (1.3 eq.) of a 20% phosgene solution in toluene were slowly added dropwise. The resulting suspension was stirred with ice bath cooling for 3 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-isocyanatopentanoate was obtained as a brown oil which was used in the subsequent reaction without further purification. Yield: 1.1 g (58% of theory).

Workup

  1. temperaturecooling for 3 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-a5c0e04dc51c4980996f719739cb91fb
Source dataset
uspto-grants-2013_12
Patent number
US08609681B2

Reaction notes

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