Acetic Acid → HCID 11988558, compound

HRID 1983545Notes

Reaction equation

HRID 1983545 reaction equation
C[Si](C)(C)Cl.C(N(CC)CC)C.C(O)(=O)C.[CH3:17][Si:18]([CH3:36])([CH3:35])[N:19]1[C@H:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C@H:21]([O:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:20]1=[O:34]>>[CH3:17][Si:18]([CH3:36])([CH3:35])[N:19]1[CH:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:21]([O:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:20]1=[O:34]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 68505438HCID 68505438, compound

Product 1

HCID 11988558HCID 11988558, compound

Procedure

A one-pot procedure for the synthesis of previously unreported N-trimethylsilyl beta-lactam from the trimethylsilyl-2-trimethylsiloxy-acetate has been discovered to be an efficient economical method not requiring cryogenic cooling. To a magnetically stirring solution of hexamethyldisilazane (390 g, 2.42 mol) in dry 1,2-dimethoxyethane (505 mL) under nitrogen with a circulation chiller at 0° C. was added a 2.5 M solution of n-butyllithium (840 mL, 2.1 mol) at a rate so as to control the exothermic reaction temperature to <30° C. (over 45 min) to generate the required LHMDS base in situ. Once the LHMDS solution temperature has reached <10° C., a neat mixture of TMSCl (119.5 g, 1.1 mol) and the trimethylsilyl-2-(trimethylsiloxy)acetate (240 g, 1.1 mol) was added over 15 minutes to give the tris(trimethylsiloxy)ethene in situ. Then neat benzaldehyde (106.12 g, 1.0 mol) was added at a rate so as to control the exothermic reaction temperature to <25° C. to give the N-trimethylsilyl-benzaldimine in situ. The mixture was allowed to react at ambient temperature (22° C.) until 1H NMR monitoring indicated that the disappearance of the ketene acetal resonance at 5.4 ppm (CDCl3) occurred at 12 h of reaction time. The reaction mixture was quenched with trimethylchlorosilane (TMSCl, 108.64 g, 1.0 mol), triethylamine (25.3 g, 0.25 mol) followed by acetic acid (6.0 g, 0.1 mol) while keeping the exothermic reaction temperature to <22° C. The mixture was diluted with hexanes (500 mL) and the resulting lithium chloride salt was filtered off through a pad of celite (200 g) followed by filter cake washing with hexanes (250 mL). The filtrate was concentrated under rotary vacuum evaporation to a residue. The residue was taken up in hexanes (500 mL) and allowed to stand at −25° C. to induce crystal formation. The white crystals were collected by vacuum filtration, washed with cold −20° C. hexanes (200 mL), and dried to a constant weight of 152 g. The filtrate was concentrated to a residue, taken up in hexanes (200 mL), and recrystallized as previous to give a second crop of 32 g. The crops were combined (184 g, 60% yield) and 1H NMR analysis found them to be pure cis-N-trimethylsilyl-3-trimethylsiloxy-4-phenyl-azetidin-2-one. Mp: 53 to 55° C. 1H NMR (400 MHz, CDCl3) δ (ppm): 0.11 (s, 9H), 0.14 (s, 9H), 4.63 (d, J=5.01 Hz, 1H), 5.06 (d, J=5.01 Hz, 1H), 7.31 (m, 5H).

Workup

  1. customto react at ambient temperature (22° C.) until 1H NMR
  2. customoccurred at 12 h of reaction time
  3. customto <22° C
  4. filtrationthe resulting lithium chloride salt was filtered off through a pad of celite (200 g)
  5. filtrationby filter cake
  6. washwashing with hexanes (250 mL)
  7. concentrationThe filtrate was concentrated under rotary vacuum evaporation to a residue
  8. customto stand at −25° C.
  9. filtrationThe white crystals were collected by vacuum filtration
  10. washwashed with cold −20° C. hexanes (200 mL)
  11. customdried to a constant weight of 152 g
  12. concentrationThe filtrate was concentrated to a residue
  13. customrecrystallized as previous
  14. customto give a second crop of 32 g

Sources & evidence

ORD record
ord-c803e6da29494db6bb8f3411d346af45
Source dataset
uspto-grants-2009_06
Patent number
US07541458B2

Reaction notes

Loading…