Tetrahydrofuran → HCID 86707748, compound

HRID 1190854Notes

Reaction equation

HRID 1190854 reaction equation
[C:1]([O:5][CH3:6])(=[O:4])[CH2:2][CH3:3].[Br:7][C:8]1[CH:17]=[CH:16][C:11]2[N:12]=[C:13](Cl)[S:14][C:10]=2[CH:9]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1>C1(C)C=CC=CC=1>[Br:7][C:8]1[CH:17]=[CH:16][C:11]2[N:12]=[C:13]([CH:2]([CH3:3])[C:1]([O:5][CH3:6])=[O:4])[S:14][C:10]=2[CH:9]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11124Methyl propionateHCID 20498716-Bromo-2-chlorobenzothiazoleHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 86707748HCID 86707748, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of methyl propionate (0.088 mL, 0.89 mmol) and 6-bromo-2-chlorobenzo[d]thiazole (221 mg, 0.89 mmol) in degassed toluene (5 mL) at brine/ice bath temperature was slowly added 1.0 M NaHMDS in THF (2.22 mL, 2.22 mmol). After the addition was complete, the reaction was stirred for 10 min. The mixture was then quenched with satd. NH4Cl (15 mL) then extracted with EtOAc (2×20 mL). The organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 0-100% EtOAc/hexane to give Compound R3a (198 mg, 0.66 mmol, 74% yield) as a yellow solid. LCMS=1.0 min using analytical method (M), 302.0 (M+H). 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J=1.8 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.58 (dd, J=8.7, 1.9 Hz, 1H), 4.30 (q, J=7.3 Hz, 1H), 3.78 (s, 3H), 1.75 (d, J=7.3 Hz, 3H).

Workup

  1. additionAfter the addition
  2. customThe mixture was then quenched with satd
  3. extractionNH4Cl (15 mL) then extracted with EtOAc (2×20 mL)
  4. dry with materialThe organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-100% EtOAc/hexane
  9. customto give Compound R3a (198 mg, 0.66 mmol, 74% yield) as a yellow solid
  10. customLCMS=1.0 min

Sources & evidence

ORD record
ord-8aebacdb23324f089ebf3bb8e1cb5d26
Source dataset
uspto-grants-2014_03
Patent number
US08680090B2

Reaction notes

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