Morpholine → HCID 70503853, compound

HRID 1679218Notes

Reaction equation

HRID 1679218 reaction equation
[CH3:1][O:2][CH2:3][S:4][CH:5]1[N:8]([C:9](=[C:23](O)[CH3:24])[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)=[O:11])[C:7](=[O:26])[CH:6]1[NH:27][C:28](=[O:37])[CH2:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CS(Cl)(=O)=O.[NH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1.[Br:49]N1C(=O)CCC1=O>O1CCCC1.O.C(N(CC)CC)C>[CH3:1][O:2][CH2:3][S:4][CH:5]1[N:8]([C:9](=[C:23]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)[CH2:24][Br:49])[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)=[O:11])[C:7](=[O:26])[CH:6]1[NH:27][C:28](=[O:37])[CH2:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[CH3:1][O:2][CH2:3][S:4][CH:5]1[N:8]([C:9](=[C:23]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)[CH3:24])[C:10]([O:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[O:11])[C:7](=[O:26])[CH:6]1[NH:27][C:28](=[O:37])[CH2:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

9

Reactant 4

HCID 8083MorpholineHCID 31297Methanesulfonyl chlorideHCID 67184N-bromobutanimideHCID 70547194p-Nitrobenzyl alpha-[4-methoxymethylthio-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-alpha-(1-hydroxyethylidene)acetate

Product 2

HCID 70503548p-Nitrobenzyl alpha-[4-methoxymethylthio-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-alpha-(1-morpholinoethylidene)acetateYield 14%HCID 70503853HCID 70503853, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 8471TriethylamineSolvent

Procedure

One dissolves p-nitrobenzyl α-[4-methoxymethylthio-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-α-(1-hydroxyethylidene)-acetate (1.06 g) in tetrahydrofuran (10 ml), cools to -40° C under nitrogen atmosphere, adds triethylamine (489 mg) dissolved in tetrahydrofuran (1 ml) and methanesulfonyl chloride (252 mg) dissolved in tetrahydrofuran (1 ml), and stirs for 30 minutes at -40° C and for 45 minutes at 0° C. To this solution, one adds morpholine (209 mg) dissolved in tetrahydrofuran (1 ml), keeps at 0° C for 2 hours, adds N-bromosuccinimide (392 mg), keeps at 0° C for 1.5 hour, adds water, and removes the separated oily material, and extracts with ethyl acetate. The extract solution and the removed oily material is combined, dried over magnesium sulfate, and evaporated. Purification of the obtained residual oil (1.4 g) by chromatography over silica gel containing 5% water (20 g) gives p-nitrobenzyl α-[4-methoxymethylthio-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-α-(1-morpholino-2-bromoethylidene)acetate (700 mg; Yield: 52%) and p-nitrobenzyl α-[4-methoxymethylthio-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-α-(1-morpholinoethylidene)acetate (170 mg; Yield: 14%).

Workup

  1. customcools to -40° C under nitrogen atmosphere
  2. waitfor 45 minutes at 0° C
  3. waitkeeps at 0° C for 2 hours
  4. waitkeeps at 0° C for 1.5 hour
  5. customremoves the separated oily material, and extracts with ethyl acetate
  6. dry with materialdried over magnesium sulfate
  7. customevaporated
  8. customPurification of the obtained residual oil (1.4 g) by chromatography over silica gel containing 5% water (20 g)

Sources & evidence

ORD record
ord-9e3ced89edc24775aa4edc6886ce3d12
Source dataset
uspto-grants-1978_03
Patent number
US04079181

Reaction notes

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