Acetic Acid → 3-t-Butyldiphenylsilyloxy-1-(4-cyano-1,3-thiazol-2-yl)azetidine

HRID 891556Notes

Reaction equation

HRID 891556 reaction equation
[Si:1]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28](OCC)=O)[N:27]=2)[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+:34].C[Al](C)C.C(O)(=O)C.C(OCC)(=O)C>C1C=CC=CC=1>[Si:1]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28]#[N:34])[N:27]=2)[CH2:20]1)([C:14]([CH3:16])([CH3:15])[CH3:17])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 222429823-t-Butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidineHCID 22243074Ammonium chloride trimethylaluminium

Product 1

HCID 222430073-t-Butyldiphenylsilyloxy-1-(4-cyano-1,3-thiazol-2-yl)azetidineYield 76%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 3-t-butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine (7.73 g, 16.6 mmol) (obtained as described in Reference Example 2(1)) in benzene (370 ml) was added a solution of 0.67M ammonium chloride-trimethylaluminium in benzene (75 ml) at room temperature under an atmosphere of nitrogen. The mixture was stirred in a water bath (50° C.) for 17 hours. After checking the completion of the reaction, 10% aqueous acetic acid solution (100 ml) and ethyl acetate (50 ml) were added to the reaction mixture in an ice bath and the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using n-hexane:ethyl acetate (3:1) as the eluant to afford 3-t-butyldiphenylsilyloxy-1-(4-cyano-1,3-thiazol-2-yl)azetidine (6.98 g, yield 76%) as a pale brown solid.

Workup

  1. customat room temperature
  2. additionwere added to the reaction mixture in an ice bath
  3. stirringthe resulting mixture was stirred at room temperature for 30 minutes
  4. extractionThe reaction mixture was extracted with ethyl acetate
  5. washThe organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-a72f4c29ce87434a828759af5f6b3cf3
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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