Hydrochloric Acid → tert-Butyl 2-(2-ethoxy-2-oxoethyl)benzo[d]thiazole-6-carboxylate

HRID 1190849Notes

Reaction equation

HRID 1190849 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:11]([O:14][CH2:15][CH3:16])(=[O:13])[CH3:12].Cl[C:18]1[S:19][C:20]2[CH:26]=[C:25]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:24]=[CH:23][C:21]=2[N:22]=1.Cl>C1COCC1.C1(C)C=CC=CC=1>[CH2:15]([O:14][C:11](=[O:13])[CH2:12][C:18]1[S:19][C:20]2[CH:26]=[C:25]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:24]=[CH:23][C:21]=2[N:22]=1)[CH3:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86707743tert-Butyl 2-chlorobenzo[d]thiazole-6-carboxylate

Product 1

HCID 86707744tert-Butyl 2-(2-ethoxy-2-oxoethyl)benzo[d]thiazole-6-carboxylateYield 67.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of sodium bis(trimethylsilyl)amide (4.9 mL of a 1M solution in THF, 4.90 mmol) in toluene (10 mL) at −78° C. was added dropwise ethyl acetate (0.26 mL, 2.7 mmol) and the mixture stirred for 1 h then a solution of Compound 188a (0.60 g, 2.2 mmol) in toluene (5 mL) was added over a 7 minute period. The resulting mixture was maintained at −78° C. for 1 h then slowly warmed to 0° C. over a period of 1.5 h. The reaction mixture was poured into a 1 N HCl solution and extracted with EtOAc. The combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-50% EtOAc/hexanes to give Compound 188b (480 mg, 67% yield) as a white solid. LCMS=2.13 min using analytical method (B), 322.0 (M+H). 1H NMR (400 MHz, CDCl3) δ 8.57-8.52 (m, 1H), 8.11 (dd, J=8.6, 1.5 Hz, 1H), 8.04-7.98 (m, 1H), 4.32-4.25 (m, 2H), 4.20 (s, 2H), 1.63 (s, 9H), 1.32 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturethen slowly warmed to 0° C. over a period of 1.5 h
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-5c5a88a8bee74bbaaf39c63b4938d9ce
Source dataset
uspto-grants-2014_03
Patent number
US08680090B2

Reaction notes

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