Cyclohexane → (S)-N-(Methylsulfonyl)-2-oxo-3-[[(phenylmethoxy)-carbonyl]amino]-1-azetidinecarboxamide

HRID 279804Notes

Reaction equation

HRID 279804 reaction equation
[O:1]=[C:2]1[C@@H:5]([NH:6][C:7](=[O:16])[O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:4][NH:3]1.C([Li])(CC)C.C1CCCCC1.[CH3:28][S:29]([N:32]=[C:33]=[O:34])(=[O:31])=[O:30].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCCC1.C(OCC)(=O)C>[CH3:28][S:29]([NH:32][C:33]([N:3]1[CH2:4][C@H:5]([NH:6][C:7]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:16])[C:2]1=[O:1])=[O:34])(=[O:31])=[O:30]

Participants

8

Reactant 5

HCID 8078CyclohexaneHCID 62657Potassium Phosphate, TribasicHCID 12668338Methanesulfonyl isocyanateHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamateHCID 178418400CID 53628100

Product 1

HCID 53997697(S)-N-(Methylsulfonyl)-2-oxo-3-[[(phenylmethoxy)-carbonyl]amino]-1-azetidinecarboxamideYield 53.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-75 °C

Procedure

A stirred suspension of (S)-(2-oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (2.20 g; see example 1C) in 60 ml of dry tetrahydrofuran under nitrogen was warmed using a water bath at 40° C. until solution occurs. The solution was cooled to -75° C., and 7.4 ml of 1.35 M sec-butyl lithium in cyclohexane (10 mmol) was added. After stirring for 2 minutes, (methylsulfonyl) isocyanate (about 1.20 g) was added. This reaction was stirred at -75° C. for 10 minutes and poured into 100 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. Ethyl acetate was added, and the pH was adjusted to 7. After several extractions with ethyl acetate, the aqueous layer was covered with ethyl acetate and adjusted to pH 2. Repeated extraction with ethyl acetate gave an acidic extract, which was dried (sodium sulfate) and evaporated to a residue (2.61 g). Chromatography of this residue on 250 g of silicAR CC-4 using dichloromethane and then 1% methanol in dichloromethane provided 1.82 g of product as a residue.

Workup

  1. temperaturewas warmed
  2. customat 40° C.
  3. stirringThis reaction was stirred at -75° C. for 10 minutes
  4. extractionAfter several extractions with ethyl acetate
  5. extractionextraction with ethyl acetate
  6. customgave an acidic extract, which
  7. dry with materialwas dried (sodium sulfate)
  8. customevaporated to a residue (2.61 g)

Sources & evidence

ORD record
ord-5d299bf7a4df478b8900ba5e5bf3ea22
Source dataset
uspto-grants-1986_05
Patent number
US04587047

Reaction notes

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