2,6-Lutidine → (3S,5S,6R,8S)-8-Allyl-3-(tert-butyl)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-8-methyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ium triflate

HRID 932242Notes

Reaction equation

HRID 932242 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([C@H:25]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)O)[CH2:9][C@:10]([CH3:24])([CH2:21][CH:22]=[CH2:23])[C:11]([NH:13][C@@H:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:15]O)=[O:12])[CH:5]=[CH:6][CH:7]=1.N1C(C)=CC=CC=1C.[F:42][C:43]([F:56])([F:55])[S:44]([O:47]S(C(F)(F)F)(=O)=O)(=[O:46])=[O:45].C(OCC)(=O)C>C(Cl)Cl.[O-]S([O-])(=O)=O.[Cu+2]>[O-:47][S:44]([C:43]([F:56])([F:55])[F:42])(=[O:46])=[O:45].[CH2:21]([C@@:10]1([CH3:24])[CH2:9][C@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[C@@H:25]([C:27]2[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][CH:32]=2)[N+:13]2[C@@H:14]([C:17]([CH3:20])([CH3:18])[CH3:19])[CH2:15][O:12][C:11]1=2)[CH:22]=[CH2:23]

Participants

7

Reactant 4

HCID 79372,6-Lutidine2×HCID 8857Ethyl AcetateHCID 67749Trifluoromethanesulfonic anhydride2×HCID 67999110(S)-2-((2R,3R)-2-(3-Chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-hydroxy-3,3-dimethylbutan-2-yl)-2-methylpent-4-enamide

Product 1

HCID 86660745(3S,5S,6R,8S)-8-Allyl-3-(tert-butyl)-6-(3-chlorophenyl)-5-(4-chlorophenyl)-8-methyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ium triflate

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-2-((2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-hydroxy-3,3-dimethylbutan-2-yl)-2-methylpent-4-enamide (Example 363, step A, 950 mg, 1.929 mmol) in DCM (19 mL) at −50° C. was added 2,6-lutidine (896 μl, 7.72 mmol) followed by trifluoromethanesulfonic anhydride solution (1M DCM, 4.34 mL, 4.34 mmol). The progress of the reaction was monitored by LC/MS. An additional charge of 450 uL (2 eq) 2,6-lutidine followed by 1.12 eq triflic anhydride (2.16 mmol, 2.16 mL of 1M solution in dichloromethane). The reaction was allowed to warm to 0° C. and then poured into sat. aq. CuSO4 solution. To the mixture was added 100 mL ethyl acetate. The layers were separated and the organic phase was washed with sat. aq. CuSO4. The combined organic layers were concentrated and purified by column chromatography on silica gel (eluent: 20 to 50% acetone in hexanes) to afford the title compound.

Workup

  1. customThe layers were separated
  2. washthe organic phase was washed with sat. aq. CuSO4
  3. concentrationThe combined organic layers were concentrated
  4. custompurified by column chromatography on silica gel (eluent: 20 to 50% acetone in hexanes)

Sources & evidence

ORD record
ord-3f133fab9cf24620b1fb4985831f7bf8
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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