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

HRID 891560Notes

Reaction equation

HRID 891560 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:29])[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[CH2:38][CH2:37][O: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[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[O:29])[N:27]=2)[CH2:22]1)([C:14]([CH3:16])([CH3:17])[CH3:15])([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 22243015Morpholine trimethylaluminium

Product 1

HCID 222427403-t-Butyldiphenylsilyloxy-1-(4-morpholinocarbonyl-1,3-thiazol-2-yl)azetidineYield 97%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To a solution of 3-t-butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine (1.0 g, 2.14 mmol) (obtained as described in Reference Example 2(1)) in benzene (50 ml) was added a solution of 0.67M morpholine-trimethylaluminium in benzene (6.42 ml) at room temperature under an atmosphere of nitrogen. The reaction mixture was heated under reflux for 2 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 then the resulting mixture was stirred at room temperature for 30 minutes. 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 n-hexane:ethyl acetate (3:1→1:3) as the eluant to afford 3-t-butyldiphenylsilyloxy-1-(4-morpholinocarbonyl-1,3-thiazol-2-yl)azetidine (1.05 g, yield 97%) as a pale brown solid.

Workup

  1. customat room temperature
  2. temperatureThe reaction mixture was heated
  3. temperatureunder reflux for 2 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-ac0bcd445a774941becee78ab403932b
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

Loading…