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

HRID 891808Notes

Reaction equation

HRID 891808 reaction equation
[Si:1]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[O:24][CH:25]=[C:26]([C:28](OC)=[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:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C[Al](C)C.C(O)(=O)C.C(OCC)(=O)C>C1(C)C=CC=CC=1>[Si:1]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[O:24][CH:25]=[C:26]([C:28]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[O:29])[N:27]=2)[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl Acetate2×HCID 222427783-t-Butyldiphenylsilyloxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)azetidineHCID 22243015Morpholine trimethylaluminium

Product 1

HCID 222428193-t-Butyldiphenylsilyloxy-1-(4-morpholinocarbonyl-1,3-oxazol-2-yl)azetidineYield 36%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 3-t-butyldiphenylsilyloxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)azetidine (1.00 g, 2.29 mmol) (obtained as described in Reference Example 70(8)) in toluene (50 ml) was added a solution of 0.67 M morpholine-trimethylaluminium in toluene (6.87 ml) at room temperature under an atmosphere of nitrogen and the mixture was stirred in an oil bath (80° C.) for 4 hours. After checking the completion of the reaction, to the reaction mixture were added 10% aqueous acetic acid (50 ml) and ethyl acetate (100 ml) in an ice bath and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added ethyl acetate. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium hydrogencarbonate 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 (1:2) as the eluant to afford 3-t-butyldiphenylsilyloxy-1-(4-morpholinocarbonyl-1,3-oxazol-2-yl)azetidine (400 mg, yield 36%) as a pale brown solid.

Workup

  1. customat room temperature
  2. customthe completion of the reaction
  3. stirringthe mixture was stirred at room temperature for 1 hour
  4. customThe mixture was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate 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-f5f783da8328401f8b4e4f42d400284e
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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