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

HRID 891602Notes

Reaction equation

HRID 891602 reaction equation
[Si:1]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28]([O:30]CC)=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.[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.C[Al](C)C.C(O)(=O)C.C(OCC)(=O)C>C1C=CC=CC=1>[Si:1]([O:18][CH:19]1[CH2:20][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28]([N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)=[O:30])[N:27]=2)[CH2:22]1)([C:14]([CH3:17])([CH3:15])[CH3:16])([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

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl Acetate2×HCID 16690458Pyrrolidine trimethylaluminiumHCID 222429823-t-Butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine

Product 1

HCID 222430113-t-Butyldiphenylsilyloxy-1-(4-pyrrolidinocarbonyl-1,3-thiazol-2-yl)azetidineYield 78%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To a solution of 3-t-butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine (1.00 g, 2.14 mmol) (obtained as described in Reference Example 2(1)) in benzene (50 ml) was added a solution of 0.67M pyrrolidine-trimethylaluminium in benzene (7.6 ml) at room temperature under an atmosphere of nitrogen. The mixture was heated under reflux for 6 hours. After checking the completion of the reaction, 10% aqueous acetic acid solution (50 ml) and ethyl acetate (100 ml) were added to the reaction mixture in an ice bath and the resulting mixture was stirred at room temperature for 2 hours. After adding ethyl acetate thereto, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using hexane:ethyl acetate (1:1) as the eluant to afford 3-t-butyldiphenylsilyloxy-1-(4-pyrrolidinocarbonyl-1,3-thiazol-2-yl)azetidine (775 mg, yield 78%) as a pale brown solid.

Workup

  1. customat room temperature
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 6 hours
  4. additionwere added to the reaction mixture in an ice bath
  5. customthe reaction mixture was partitioned between ethyl acetate and water
  6. washThe organic layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-74e6413a6f514834ab7dc24beb21fefb
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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