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 67836

반응식

HRID 67836 반응식
[O:1]([CH2:8][C:9]1[S:15][CH:14]2[CH:11]([C:12](=[O:33])[N:13]2[C:16](=C(O)C)[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)=[O:18])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O.O(CC1S[CH:52]2[CH:49](C(=O)[N:51]2[C:54](=C(OS(C)(=O)=O)C)[C:55]([O:57][CH2:58][C:59]2C=CC([N+]([O-])=O)=CC=2)=O)N=1)C1C=CC=CC=1.N1CCOCC1>O1CCCC1.C(N(CC)CC)C>[O:1]([CH2:8][C:9]1[S:15][CH:14]2[CH:11]([C:12](=[O:33])[N:13]2[C:16](=[C:52]([N:51]2[CH2:54][CH2:55][O:57][CH2:58][CH2:59]2)[CH3:49])[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)=[O:18])[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

7

반응물 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 70504145p-Nitrobenzyl alpha-[3-phenoxymethyl-7-oxo4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(1-hydroxyethylidene)acetate

생성물 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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

실험 절차

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 at -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-morpholinoethylidene)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%).

후처리

  1. waitfor 2 hours at 0° C.

출처 및 근거

ORD 기록
ord-f440f9df307146cdab536ecb6b055ed3
출처 데이터셋
uspto-grants-1982_08
특허 번호
US04346218

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