2,6-Lutidine → HCID 68770353, compound

HRID 2265229Notes

Reaction equation

HRID 2265229 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([OH:14])[C@@H:9]([CH3:13])[C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])(=O)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CO>[C:32]([Si:29]([CH3:31])([CH3:30])[O:14][C@@H:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[C@@H:9]([CH3:13])[C:10]([OH:12])=[O:11])([CH3:35])([CH3:34])[CH3:33]

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 11430Potassium CarbonateHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 68768818HCID 68768818, compound

Product 1

HCID 68770353HCID 68770353, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (2R,3R)-3-(4-chloro-phenyl)-3-hydroxy-2-methyl-propionic acid (0.76 g, 3.5 mmol) in DCM (20 mL) was cooled to 0° C. and treated with 2,6-lutidine (1.24 mL, 10.6 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate (1.9 mL, 8.27 mmol). The reaction solution was stirred at 0° C. for 30 min then allowed to warm to rt and stir 1 h. The reaction was quenched with 1 M HCl and the mixture was extracted with DCM (3×). The combined organic layers were dried (Na2SO4) and concentrated to give the crude bis-silylated ester. The silyl ester was stirred in MeOH (10 mL) at rt and treated with 5% aq. K2CO3 (5 mL). The mixture was stirred 3 h, then was concentrated, diluted with 1 N HCl, and extracted with DCM (4×). The combined organic layers were dried (Na2SO4) and concentrated to give the crude acid, which was used without further purification (1.06 g, 91%). 1H NMR (400 MHz, CDCl3): 7.32-7.27 (m, 2H), 7.27-7.22 (m, 2H), 5.01 (d, J=5.3, 1H), 2.70 (dq, J=7.2, 5.6, 1H), 1.11 (d, J=6.8, 3H), 0.88 (s, 9H), 0.03 (s, 3H), −0.18 (s, 3H).

Workup

  1. temperatureto warm to rt
  2. stirringstir 1 h
  3. customThe reaction was quenched with 1 M HCl
  4. extractionthe mixture was extracted with DCM (3×)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. concentrationconcentrated
  7. customto give the crude bis-silylated ester
  8. stirringThe mixture was stirred 3 h
  9. concentrationwas concentrated
  10. additiondiluted with 1 N HCl
  11. extractionextracted with DCM (4×)
  12. dry with materialThe combined organic layers were dried (Na2SO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-55667317eb2d43a484c067b277e268aa
Source dataset
uspto-grants-2010_12
Patent number
US07855292B2

Reaction notes

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