Ammonium Chloride → (3S,4R)-4-[(1-Ethyl-5-methylpyrazol-3-yl)carbonylmethyl]-3-[(R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-one

HRID 1825348Notes

Reaction equation

HRID 1825348 reaction equation
[C:1]([C:4]1[CH:8]=[C:7]([CH3:9])[N:6]([CH2:10][CH3:11])[N:5]=1)(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C(O[C@H:26]1[NH:29][C:28](=[O:30])[C@@H:27]1[C@H:31]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH3:32])(=O)C.[Cl-].[NH4+]>O.C(OCC)(=O)C.C1COCC1>[CH2:10]([N:6]1[C:7]([CH3:9])=[CH:8][C:4]([C:1]([CH2:2][C@H:26]2[NH:29][C:28](=[O:30])[C@@H:27]2[C@H:31]([O:33][Si:34]([C:37]([CH3:38])([CH3:40])[CH3:39])([CH3:36])[CH3:35])[CH3:32])=[O:3])=[N:5]1)[CH3:11]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 10935078AzetidonHCID 221453691-(1-Ethyl-5-methyl-1H-pyrazol-3-yl)ethanone

Product 1

HCID 10691156(3S,4R)-4-[(1-Ethyl-5-methylpyrazol-3-yl)carbonylmethyl]-3-[(R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-oneYield 41.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Acetyl-1-ethyl-5-methylpyrazole (3.51 g) in dry tetrahydroturan (THF) (150 ml) under an argon atmosphere was cooled in an acetone/solid carbon dioxide bath and then treated with a 1M solution of lithium bis(trimethylsilyl)amide (50 ml). The mixture was stirred for 45 minutes and then (3R,4R)-4-acetoxy-3-[(1R)-1-tert-butyldimethylsilyloxyethyl]azetidinone (6.6 g) was added as a solid under a blanket of argon. The mixture was stirred in the cold for 3.5 h. Saturated aqueous ammonium chloride was then added, followed by ethyl acetate, and the mixture was allowed to warm to room temperature. A little water was added and the layers were separated and the aqueous layer was re-extracted with ethyl acetate. The combined ethyl acetate extracts were washed with saturated brine, dried and evaporated. Chromatography on silica gel, eluting with ethyl acetate/hexane mixtures gave the title compound (3.65 g), υmax (CH2Cl2) 3411, 1761, 1678, 1376, 1151, and 838 cm−1; δ(CDCl3) 0.064 (6H, s), 0.86 (9H, s), 1.20 (3H,d, J 6.3 Hz), 1.44 (3H, t, J 7.3 Hz), 2.31 (3H, s), 2.89 (1H, dd, J 1.8 & 4.9 Hz), 3.15 (1H, dd, J 10.0 & 17.1 Hz), 3.50 (1H, dd, J3.5 & 17.0 Hz), 4.06-4.25 (4H, m), 6.11 (1H, s), 6.53 (1H, s), (Found m/z 379.2296. C19H33N3O3Si requires m/z 379.2291),

Workup

  1. stirringThe mixture was stirred in the cold for 3.5 h
  2. customthe layers were separated
  3. extractionthe aqueous layer was re-extracted with ethyl acetate
  4. washThe combined ethyl acetate extracts were washed with saturated brine
  5. customdried
  6. customevaporated
  7. washChromatography on silica gel, eluting with ethyl acetate/hexane mixtures

Sources & evidence

ORD record
ord-c85304adfcbb41c883289d75930e75e9
Source dataset
uspto-grants-2006_05
Patent number
US07045619B2

Reaction notes

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