Acetic Acid → 3-t-Butyldiphenylsilyloxy-1-[4-(3-methoxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]azetidine

HRID 891812Notes

Reaction equation

HRID 891812 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.[CH3:32][O:33][CH:34]1[CH2:37][NH:36][CH2:35]1.C[Al](C)C.C(O)(=O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Si:1]([O:18][CH:19]1[CH2:20][N:21]([C:23]2[O:24][CH:25]=[C:26]([C:28]([N:36]3[CH2:37][CH:34]([O:33][CH3:32])[CH2:35]3)=[O:29])[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

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 134019963-MethoxyazetidineHCID 16682925TrimethylaluminumHCID 222427783-t-Butyldiphenylsilyloxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)azetidine

Product 1

HCID 222428403-t-Butyldiphenylsilyloxy-1-[4-(3-methoxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]azetidineYield 90%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 3-t-butyldiphenylsilyloxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)azetidine (1.57 g, 3.60 mmol) (obtained as described in Reference Example 70(8)) in toluene (80 ml) was added a solution of 0.67 M 3-methoxyazetidine (obtained as described in Reference Example 31(2))-trimethylaluminium in toluene (10.8 ml) at room temperature under an atmosphere of nitrogen and the mixture was stirred in an oil bath (60° C.) for 30 minutes. After checking the completion of the reaction, to the reaction mixture were added 10% aqueous acetic acid (100 ml) and ethyl acetate (200 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 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 ethyl acetate as the eluant to afford 3-t-butyldiphenylsilyloxy-1-[4-(3-methoxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]azetidine (1.50 g, yield 90%) 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 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-0c55e63bf71b438e8cee171d3c525d21
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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