N,N-Diethyl-1,1,2,3,3,3-hexafluoropropylamine → (4S,5R)-3-propionyl-2,2-dimethyl-4-fluoromethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine

HRID 507886Notes

Reaction equation

[C:1]([N:5]1[C@H:9]([CH2:10]O)[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:23])[CH3:22])(=[O:4])[CH2:2][CH3:3].C(N(CC)C(F)(F)C(F)C(F)(F)[F:30])C>C(Cl)Cl>[C:1]([N:5]1[C@H:9]([CH2:10][F:30])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:23])[CH3:22])(=[O:4])[CH2:2][CH3:3]

Participants

Conditions

Temperature: 22.5 °C

Procedure

(4R,5R)-3-propionyl-2,2-dimethyl-4-hydroxymethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound V: R1 is methylsulfonyl, R2 and R3 are methyl and R4 is ethyl) (70 g, 0.2050 moles) in methylene chloride (450 ml) reacts with N,N-diethyl-1,1,2,3,3,3-hexafluoro-1-propanamine (Ishikawa Reagent) (73.2 g, 0.328 moles) at 95-105° C. for 2-4 hours. Cooling to 20-25° C., quenching with 25% aqueous sodium hydroxide and water (2000 mL) and separation of the methylene chloride layer gives a solution of (4S,5R)-3-propionyl-2,2-dimethyl-4-fluoromethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound IX: R1 is methylsulfonyl, R2 and R3 are methyl and R4 is ethyl) for use in the next step.

Workup

customquenching with 25% aqueous sodium hydroxide and water (2000 mL) and separation of the methylene chloride layer

Sources & evidence

ORD record: ord-e33f904552324abdb82023dcd86bd5ae
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786329B2

Reaction notes

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