Morpholine → p-Nitrobenzyl alpha-(3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo(3,2,0)hept-2-en-6-yl)-alpha-(1-morpholinoethylidene)acetate

HRID 971515Notes

Reaction equation

HRID 971515 reaction equation
O(CC1S[CH:14]2[CH:11](C(=O)[N:13]2[C:16](=C(O)C)[C:17]([O-:19])=O)N=1)C1C=CC=CC=1.CS(Cl)(=O)=O.[O:29]([CH2:36][C:37]1[S:43][CH:42]2[CH:39]([C:40](=[O:65])[N:41]2[C:44](=[C:58](OS(C)(=O)=O)[CH3:59])[C:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][C:52]([N+:55]([O-:57])=[O:56])=[CH:51][CH:50]=2)=[O:46])[N:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.N1CCOCC1>O1CCCC1.C(N(CC)CC)C>[O:29]([CH2:36][C:37]1[S:43][CH:42]2[CH:39]([C:40](=[O:65])[N:41]2[C:44](=[C:58]([N:13]2[CH2:16][CH2:17][O:19][CH2:11][CH2:14]2)[CH3:59])[C:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][C:52]([N+:55]([O-:57])=[O:56])=[CH:51][CH:50]=2)=[O:46])[N:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 31297Methanesulfonyl chlorideHCID 54062639p-Nitrobenzyl alpha-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(1-methanesulfonyloxyethylidene)acetateHCID 178468116HCID 178468116, compound

Product 1

HCID 54060416p-Nitrobenzyl alpha-(3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo(3,2,0)hept-2-en-6-yl)-alpha-(1-morpholinoethylidene)acetate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

One dissolves p-nitrobenzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl -α-(1-hydroxyethylidene)acetate (940 mg) in tetrahydrofuran (14 ml), adds triethylamine (0.61 ml) and methanesulfonyl chloride (0.172 ml), and stirs for 1 hour ε+ -15° to -20° C. To the produced solution of p-nitrobenzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-methanesulfonyloxyethylidene)acetate, one adds morpholine (0.209 ml), stirs for 1.5 hours at -15° to -20° C., and for 2 hours at 0° C., to give a solution of p-nitrobenzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-morpholinoethylidene)acetate, cools to -15° C., adds pyridine (0.174 ml) followed by after 5 minutes a solution of bromine in carbon tetrachloride (1 mole/liter: 2.1 ml), stirs for 15 minutes at the same temperature, pours into water (50 ml), and extracts with ethyl acetate (50 ml). The extract solution is washed with water, dried over magnesium sulfate, and evaporated to give residue (1.7 g). Purification of the residue by chromatography over silica gel containing 10% water gives from the fractions eluted with a mixture of benzene and ethyl acetate (2:1) p-nitrobenzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(2-bromo-1-morpholinoethylidine)acetate (1.109 g; Yield: 89.7%) and p-nitrobenzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(2-bromo-1-morpholinoethyl)-α-methanesulfonylacetate (85 mg; Yield: 7.7%).

Workup

  1. waitfor 2 hours at 0° C.

Sources & evidence

ORD record
ord-b60e7895e3c0434fac21572dfa2e4797
Source dataset
uspto-grants-1979_07
Patent number
US04160085

Reaction notes

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