Sodium hydride → N-(6-Phenylhexanoyl)-(4-benzylthio-2-oxoazetidin-yl)acetamide

HRID 1603661Notes

Reaction equation

HRID 1603661 reaction equation
[CH2:1]([S:8][CH:9]1[N:12]([CH2:13][C:14]([NH2:16])=[O:15])[C:11](=[O:17])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na].[C:19]1([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30](Cl)=[O:31])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[H-].[Na+]>C1COCC1>[C:19]1([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]([NH:16][C:14](=[O:15])[CH2:13][N:12]2[CH:9]([S:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:10][C:11]2=[O:17])=[O:31])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 5360545SodiumHCID 135978376-Phenylhexanoyl chloride2×HCID 19605267(4-Benzylthio-2-oxoazetidin-1-yl)acetamide

Product 1

HCID 19605348N-(6-Phenylhexanoyl)-(4-benzylthio-2-oxoazetidin-yl)acetamideYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-10 °C

Procedure

A solution of (4-benzylthio-2-oxoazetidin-1-yl)acetamide (0.63 g, 2.52 mmol) in dry THF (15 ml) was added to a suspension of sodium hyride (60% in oil, 0.10 g, 2.5 mmol) in dry THF at -10° C. under a nitrogen atmosphere. The reaction was stirred at -10° C. for 10 minutes and was then treated with a solution of 6-phenylhexanoyl chloride (0.58 g, 2.75 mmol) in dry THF (5 ml) dropwise over 2 minutes maintaining the temperature at -10° C. The cooling bath was removed an after stirring for 60 minutes the reaction was treated with sodium hydride (50 mg, 1.25 mmol) and 6-phenylhexanoyl chloride (0.29 g, 1.38 mmol) in dry THF (2 ml). The reaction was stirred for 60 minutes, poured into ice/brine (100 ml), extracted with ethyl acetate (2×50 ml). The organic extracts were combined, washed with aq. sat. NaHCO3 solution, brine, dried (MgSO4) and evaporated under reduced pressure to an orange oil. Purification by repeated column chromatography eluted with hexane:ethyl acetate (3:1 to 1:1) gave the product as a colourless oil (0.22 g, 21% yield, contains 10% 6-phenylhexanoic acid) 1H nmr δ (CDCl3) 1.3-1.7 (6H, m, 3×CH2), 2.44 (2H, t, J=7.4 Hz, NHCOCH2), 2.62 (2H, t, J=7.6 Hz, PhCH2), 2.96, 3.02 (1H, dd, J=2.4, 15.3 Hz, H3), 3.39, 3.45 (1H, dd, J=5.1, 15.3 Hz, H3), 3.61, 4.32 (each 1H, d, J=18.8 Hz, NCH2CO), 3.76 (2H, m, SCH2), 4.9 (1H, m, H4), 7.1-7.3 (10H, m, 2×Ph--H), 8.17 (1H, m, NH)

Workup

  1. temperaturemaintaining the temperature at -10° C
  2. customThe cooling bath was removed
  3. stirringan after stirring for 60 minutes the reaction
  4. stirringThe reaction was stirred for 60 minutes
  5. extractionextracted with ethyl acetate (2×50 ml)
  6. washwashed with aq. sat. NaHCO3 solution, brine
  7. dry with materialdried (MgSO4)
  8. customevaporated under reduced pressure to an orange oil
  9. customPurification
  10. washeluted with hexane:ethyl acetate (3:1 to 1:1)

Sources & evidence

ORD record
ord-c9dcc51d6f964276af2da492dc1d66de
Source dataset
uspto-grants-1999_11
Patent number
US05990102

Reaction notes

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