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

HRID 976993Notes

Reaction equation

HRID 976993 reaction equation
[C:1]([C:4]1[CH:8]=[C:7]([CH2:9][CH3:10])[N:6]([CH2:11][CH3:12])[N:5]=1)(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C(O[C@H:27]1[NH:30][C:29](=[O:31])[C@@H:28]1[C@H:32]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH3:33])(=O)C.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[CH2:11]([N:6]1[C:7]([CH2:9][CH3:10])=[CH:8][C:4]([C:1]([CH2:2][C@H:27]2[NH:30][C:29](=[O:31])[C@@H:28]2[C@H:32]([O:34][Si:35]([C:38]([CH3:39])([CH3:41])[CH3:40])([CH3:37])[CH3:36])[CH3:33])=[O:3])=[N:5]1)[CH3:12]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 10935078AzetidonHCID 221454071-(1,5-Diethyl-1H-pyrazol-3-yl)ethanone

Product 1

HCID 10739360(3S,4R)-4-[(1,5-Diethylpyrazol-3-yl)carbonylmethyl]-3-[(R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-oneYield 46.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

3-Acetyl-1,5-diethylpyrazole (1.65 g) in dry tetrahydrofuran (THF) (50 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 (19.8 ml). The mixture was stirred for 45 minutes and then (3R,4R)-4-acetoxy-3-[(R)-1-tert-butyldimethylsilyloxyethyl]azetidinone (2.84 g) in dry THF (10 ml), added by syringe over ca. 1 minute. The mixture was stirred in the cold for 5 h. Saturated aqueous ammonium chloride was then added, followed by ethyl acetate. The layers were separated and the aqueous layer was re-extracted with ethyl acetate. The combined ethyl acetate layers were washed with saturated brine. dried and evaporated. Chromatography on silica gel, eluting with ethyl acetate/hexane mixtures gave the title compound (1.82 g); νmax (CH2Cl2) 3412, 2957, 2885, 2857, 1761, 1677, 1473, and 1376 cm-1 ; δ (CDCl3) 0.078 (6H, s), 0.88 (9H, s), 1.21 (3H,d, J 6.3 Hz), 1.29 (3H, t, J 7.6 Hz), 1.45 (3H, t, J 7.3 Hz), 2.63 (2H, q, J 7.3 Hz), 2.90 (1H, dd, J 1.6 & 4.9 Hz), 3.15 (1H, dd, J 10.0 & 17.0 Hz), 3.50 (1H, dd, J 3.6 & 17.0 Hz), 4.06-4.25 (4H, m), 6.09 (1H, s), 6.56 (1H, s). (Found m/z 393.2445. C20H35N3O3Si requires m/z 393.2448).

Workup

  1. stirringThe mixture was stirred in the cold for 5 h
  2. customThe layers were separated
  3. extractionthe aqueous layer was re-extracted with ethyl acetate
  4. washThe combined ethyl acetate layers 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-70c78ee6ef0747bd9a95cf5cd19c0950
Source dataset
uspto-grants-1997_03
Patent number
US05612477

Reaction notes

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