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

HRID 891552
Notes
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Reaction equation

HRID 891552 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.[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[CH2:20][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28](=[O:30])[NH2:34])[N:27]=2)[CH2:22]1)([C:14]([CH3:15])([CH3:16])[CH3:17])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl Acetate2×HCID 222429823-t-Butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidineHCID 22243074Ammonium chloride trimethylaluminium

Product 1

HCID 222429383-t-Butyldiphenylsilyloxy-1-(4-carbamoyl-1,3-thiazol-2-yl)azetidineYield 91%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of 3-t-butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine (5.85 g, 12.5 mmol) (obtained as described in Reference Example 2(1)) in benzene (290 ml) was added a solution of 0.67M ammonium chloride-trimethylaluminium in benzene (56.4 ml) at room temperature under an atmosphere of nitrogen. The mixture was stirred in a water bath (40° 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 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 toluene:acetonitrile (3:1→1:2) as the eluant to afford 3-t-butyldiphenylsilyloxy-1-(4-carbamoyl-1,3-thiazol-2-yl)azetidine (4.97 g, yield 91%) 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 2 hours
  4. customthe reaction mixture was partitioned between ethyl acetate and water
  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 sodium 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-8c4fc420e1764eed894736e21d0b40f8
Source dataset
uspto-grants-2006_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07001897B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes