Boron trifluoride etherate → HCID 86697901, compound

HRID 1618992Notes

Reaction equation

HRID 1618992 reaction equation
[CH3:1][Si:2]([CH3:9])([CH3:8])[C:3]1[S:4][CH:5]=[CH:6][N:7]=1.C([Li])CCC.B(F)(F)F.CCOCC.[N:24]1[O:25][CH2:26][C@@H:27]2[CH2:31][N:30]([C:32]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:33])[CH2:29][C:28]=12>O1CCCC1.C1(C)C=CC=CC=1>[CH3:1][Si:2]([CH3:9])([CH3:8])[C:3]1[S:4][C:5]([C:28]23[CH2:29][N:30]([C:32]([O:34][CH2:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[O:33])[CH2:31][CH:27]2[CH2:26][O:25][NH:24]3)=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 8000Boron trifluoride etherateHCID 5884532-TrimethylsilylthiazoleHCID 86697902HCID 86697902, compoundHCID 178418339Butyllithium

Product 1

HCID 86697901HCID 86697901, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A −78° C. solution of 2-trimethylsilylthiazole (383 mg, 2.44 mmol) in tetrahydrofuran (3 mL) is treated drop wise with a solution of n-butyl lithium (1.52 mL, 2.44 mmol, 1.6 M hexanes) and the reaction is stirred at −78° C. for 10 minutes to give a thick orange slurry. The slurry is treated with boron trifluoride etherate (205 μL, 1.62 mmol) to give a red mixture and then a solution of benzyl (3aR)-3,3a,4,6-tetrahydropyrrolo[3,4-c]isoxazole-5-carboxylate (200 mg, 812 μmol) is added immediately in toluene (2 mL) to this mixture. The resultant mixture is stirred at −78° C. for 20 minutes under nitrogen. The reaction is quenched with saturated ammonium chloride and warmed to room temperature. Water and saturated sodium bicarbonate is added and the mixture is extracted with ethyl acetate (3×). The combined organic layers are dried over sodium sulfate and the solvent is removed under vacuum. The crude product is purified over silica gel eluting with 5% to 100% ethyl acetate in hexanes gradient, to give the title compound (245 mg, 75%). ES/MS (m/e): 404(M+H).

Workup

  1. customto give a thick orange slurry
  2. customto give a red mixture
  3. customThe reaction is quenched with saturated ammonium chloride
  4. temperaturewarmed to room temperature
  5. additionWater and saturated sodium bicarbonate is added
  6. extractionthe mixture is extracted with ethyl acetate (3×)
  7. dry with materialThe combined organic layers are dried over sodium sulfate
  8. customthe solvent is removed under vacuum
  9. customThe crude product is purified over silica gel eluting with 5% to 100% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-8f37bcef18904408aacf0a7bec2b71a6
Source dataset
uspto-grants-2014_07
Patent number
US08772282B2

Reaction notes

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