Acetic Acid → HCID 69583523, compound

HRID 891662Notes

Reaction equation

HRID 891662 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.[Si:33]([O:50][CH2:51][C@@H:52]([NH2:57])[C@@H:53]([CH3:56])[CH2:54][CH3:55])([C:46]([CH3:49])([CH3:48])[CH3:47])([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C[Al](C)C.C(O)(=O)C.C(OCC)(=O)C>C1C=CC=CC=1>[Si:1]([O:18][CH:19]1[CH2:22][N:21]([C:23]2[S:24][CH:25]=[C:26]([C:28](=[O:29])[NH:57][C@H:52]([CH2:51][O:50][Si:33]([C:46]([CH3:48])([CH3:47])[CH3:49])([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C@@H:53]([CH3:56])[CH2:54][CH3:55])[N:27]=2)[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl Acetate2×HCID 222429823-t-Butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidineHCID 23598349HCID 23598349, compound

Product 1

HCID 69583523HCID 69583523, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

Subsequently, to a solution of 3-t-butyldiphenylsilyloxy-1-(4-ethoxycarbonyl-1,3-thiazol-2-yl)azetidine (2.00 g, 4.29 mmol) (obtained as described in Reference Example 2(1)) in benzene (100 ml) was added a solution of 0.67M (1S,2S)-1-(t-butyldiphenylsilyloxymethyl)-2-methylbutylamine-trimethylaluminium in benzene (12.9 ml) at room temperature under an atmosphere of nitrogen. The mixture was heated under reflux overnight. After checking the completion of the reaction, 10% aqueous acetic acid solution (100 ml) and ethyl acetate (200 ml) were added to the reaction mixture in an ice bath, and the resulting mixture was stirred at room temperature for 30 minutes. 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 n-hexane:ethyl acetate (6:1→1:3) as the eluant to afford 3-t-butyldiphenylsilyloxy-1-{4-[(1S,2S)-1-(t-butyldiphenylsilyloxymethyl)-2-methylbutylcarbamoyl]-1,3-thiazol-2-yl}azetidine (1.89 g, yield 57%) as a pale brown solid.

Workup

  1. customat room temperature
  2. temperatureThe mixture was heated
  3. temperatureunder reflux overnight
  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-04690c8bb05a42ac891c31596e65a213
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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