2-Trimethylsilylthiazole → (+/-) 3-((1,3-Thiazol-2-yl)hydroxymethyl)-1-azabicyclo [2.2.2]octane

HRID 1534885Notes

Reaction equation

HRID 1534885 reaction equation
[N:1]12[CH2:8][C:5]([C:9]([O:11]CC)=O)([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2.C[Si](C)(C)[C:16]1[S:17][CH:18]=[CH:19][N:20]=1.O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[S:17]1[CH:18]=[CH:19][N:20]=[C:16]1[CH:9]([OH:11])[CH:5]1[CH:4]2[CH2:3][CH2:2][N:1]([CH2:7][CH2:6]2)[CH2:8]1

Participants

5

Reactant 3

HCID 5884532-TrimethylsilylthiazoleHCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 15663615Ethyl 1-azabicyclo[3.2.1]octane-5-carboxylate

Product 1

HCID 19370570(+/-) 3-((1,3-Thiazol-2-yl)hydroxymethyl)-1-azabicyclo [2.2.2]octane

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (±) 3-formyl-1-azabicyclo[2.2.2]octane (D32) (2 5g, 0.018 moles) and 2-trimethylsilyl-1,3-thiazole (2.7g, 0.017 moles) was stirred together without solvent at room temperature for 3h. The mixture was diluted with tetrahydrofuran (100ml) and then treated with tetrabutylammonium fluoride trihydrate (5.4g, 0.017 moles). After 1h the mixture was concentrated in vacuo and the residue partitioned between saturated potassium carbonate solution and chloroform. The organic layer was dried (Na2SO4) and evaporated to dryness. The residue was subjected to column chromatography on TLC alumina eluting with 0.5% methanol/chloroform. This gave an oil which was triturated with diethylether/methanol to yield the title compound (D33) as a buff solid (0.5g, 13%).

Workup

  1. concentrationAfter 1h the mixture was concentrated in vacuo
  2. customthe residue partitioned between saturated potassium carbonate solution and chloroform
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. customevaporated to dryness
  5. customThis gave an oil which
  6. customwas triturated with diethylether/methanol

Sources & evidence

ORD record
ord-a3d4b2d239a64e58b77d29fe98ac89ba
Source dataset
uspto-grants-1992_02
Patent number
US05091397

Reaction notes

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