tert-Butyl acetate → 2-Benzothiazoleacetic acid, 4-chloro-, 1,1-dimethylethyl ester

HRID 2206322Notes

Reaction equation

HRID 2206322 reaction equation
[C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Cl[C:20]1[S:21][C:22]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:23]=2[N:24]=1>C1COCC1>[Cl:29][C:25]1[C:23]2[N:24]=[C:20]([CH2:2][C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:3])[S:21][C:22]=2[CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 771772,4-DichlorobenzothiazoleHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 717441262-Benzothiazoleacetic acid, 4-chloro-, 1,1-dimethylethyl esterYield 99.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1-Liter, 3-necked round bottomed flask fitted with a nitrogen inlet, a 500 mL addition funnel and a septum stopper was charged with t-butyl acetate (26.8 mL, 200 mmol) and anhydrous THF (50 mL). Upon cooling in a dry ice-acetone bath, to the mixture was added lithium bis(trimethylsilyl)amide (1M, THF solution) (200 mL, 200 mmol) via syringe over 15 min. After stirring at that temperature for 30 minutes, to the mixture was added a solution of 2,4-dichloro-benzothiazole (8.15 g, 40 mmol) in THF (100 mL) from the addition funnel over 15 minutes. The cooling bath was removed allowing the reaction to warm to room temperature over 1 hour. The reaction mixture was concentrated, then diluted with EtOAc and a saturated NaHCO3 solution. The organic layer was separated and the aqueous layer was extracted with EtOAc twice. The combined organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography on silica gel eluting with a gradient mixture of EtOAc/hexanes to give 11.28 g (99%) of the title compound as a yellow solid. 1H-NMR (500 MHz, DMSO-d6) δ (ppm) 8.00 (1H, dd, J=1.0, 8.0 Hz), 7.53 (1H, dd, J=1.0, 8.0 Hz), 7.36 (1H, t, J=8.0 Hz), 4.19 (2H, s), 1.38 (9H, s).

Workup

  1. customA 1-Liter, 3-necked round bottomed flask fitted with a nitrogen inlet, a 500 mL addition funnel
  2. temperatureUpon cooling in a dry ice-acetone bath, to the mixture
  3. customThe cooling bath was removed
  4. customthe reaction
  5. concentrationThe reaction mixture was concentrated
  6. additiondiluted with EtOAc
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with EtOAc twice
  9. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by column chromatography on silica gel eluting with a gradient mixture of EtOAc/hexanes

Sources & evidence

ORD record
ord-b2110d01604f4aaab3b650d061917696
Source dataset
uspto-grants-2016_06
Patent number
US09371336B2

Reaction notes

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