Triethylamine → HCID 22243013, compound

HRID 891760Notes

Reaction equation

HRID 891760 reaction equation
[N:1]([CH2:4][CH2:5][N:6]([CH:18]([CH3:20])[CH3:19])[C:7]([C:9]1[N:10]=[C:11]([N:14]2[CH2:17][CH2:16][CH2:15]2)[S:12][CH:13]=1)=[O:8])=[N+]=[N-].[Si:21]([O:38]C1CNC1)([C:34]([CH3:37])([CH3:36])[CH3:35])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[N+:43]([C:46]1[CH:56]=[CH:55][C:49]([CH2:50][O:51][C:52](Cl)=[O:53])=[CH:48][CH:47]=1)([O-:45])=[O:44].C(N(CC)CC)C>CO.[OH-].[OH-].[Pd+2]>[Si:21]([O:38][CH:16]1[CH2:17][N:14]([C:11]2[S:12][CH:13]=[C:9]([C:7](=[O:8])[N:6]([CH:18]([CH3:20])[CH3:19])[CH2:5][CH2:4][NH:1][C:52]([O:51][CH2:50][C:49]3[CH:48]=[CH:47][C:46]([N+:43]([O-:45])=[O:44])=[CH:56][CH:55]=3)=[O:53])[N:10]=2)[CH2:15]1)([C:34]([CH3:37])([CH3:35])[CH3:36])([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 782054-Nitrobenzyl chloroformateHCID 131725369HCID 131725369, compound

Product 1

HCID 22243013HCID 22243013, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

A solution of 1-{4-[N-(2-azido-ethyl)-N-isopropyl-carbamoyl]-1,3-thiazol-2-yl}azetidine-3-t-butyldiphenylsilyloxyazetidine (1.33 g, 2.42 mmol) (obtained as described in Reference Example 60(1)) in methanol (65 ml) was subjected to catalytic hydrogenation in the presence of 20% palladium hydroxide on charcoal (1.33 g) at room temperature. After checking the completion of the reaction, the reaction mixture was filtered in order to remove the catalyst and the filtrate concentrated under reduced pressure. To a solution of the obtained crude product in methylene chloride (63 ml) were added chloroformic acid p-nitrobenzyl ester (627 mg, 2.90 mmol) and triethylamine (0.41 ml, 2.90 mmol) in an ice bath, and the mixture was stirred for 1 hour under the same conditions. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium chloride solution. The obtained organic layer was 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 ethyl acetate:methanol (10:1) as the eluant to afford 3-t-butyldiphenylsilyloxy-1-(4-{N-isopropyl-N-[2-(p-nitrobenzyloxycarbonylamino)ethyl]-carbamoyl}-1,3-thiazol-2-yl)azetidine (945 mg, yield 56%) as a pale yellow oil.

Workup

  1. customthe completion of the reaction
  2. filtrationthe reaction mixture was filtered in order
  3. customto remove the catalyst
  4. concentrationthe filtrate concentrated under reduced pressure
  5. customTo a solution of the obtained crude product in methylene chloride (63 ml)
  6. customthe completion of the reaction
  7. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium chloride solution
  8. dry with materialThe obtained organic layer was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-0e9d7868366245a9b9f70ac2b6035f37
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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