Acetic Acid → 1-[4-(3-t-Butyldiphenylsilyloxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]-3-hydroxyazetidine

HRID 891816Notes

Reaction equation

HRID 891816 reaction equation
[OH:1][CH:2]1[CH2:5][N:4]([C:6]2[O:7][CH:8]=[C:9]([C:11]([O:13]C)=O)[N:10]=2)[CH2:3]1.[Si:15]([O:32][CH:33]1[CH2:36][NH:35][CH2:34]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C[Al](C)C.C(O)(=O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Si:15]([O:32][CH:33]1[CH2:34][N:35]([C:11]([C:9]2[N:10]=[C:6]([N:4]3[CH2:3][CH:2]([OH:1])[CH2:5]3)[O:7][CH:8]=2)=[O:13])[CH2:36]1)([C:28]([CH3:31])([CH3:29])[CH3:30])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 16682925TrimethylaluminumHCID 178425313-((Tert-butyldiphenylsilyl)oxy)azetidineHCID 222430383-Hydroxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)azetidine

Product 1

HCID 222429771-[4-(3-t-Butyldiphenylsilyloxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]-3-hydroxyazetidineYield 100%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 3-hydroxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)azetidine (500 mg, 2.52 mmol) (obtained as described in Reference Example 70(7)) in toluene (25 ml) was added a solution of 0.67 M 3-t-butyldiphenylsilyloxyazetidine (obtained as described in Reference Example 42(2))-trimethylaluminium in toluene (11.3 ml) at room temperature under an atmosphere of nitrogen and the mixture was stirred in an oil bath (80° C.) for 15 minutes. After checking the completion of the reaction, to the reaction mixture were added 10% aqueous acetic acid (20 ml) and ethyl acetate (50 ml) in an ice bath and the mixture was stirred at room temperature for 0.5 hours. 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 methylene chloride:methanol (95:5→9:1) as the eluant to afford 1-[4-(3-t-butyldiphenylsilyloxyazetidine-1-carbonyl)-1,3-oxazol-2-yl]-3-hydroxyazetidine (1.24 g, yield 100%) 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 0.5 hours
  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-7dd6628eb5d94cd796b2a77ba0bdbec2
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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