6-Aminopenicillanic acid → Amoxicillin

HRID 1701482Notes

Reaction equation

[K].[OH:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([NH:13]C(C(OC)=O)C=C)[C:10]([OH:12])=O)=[CH:5][CH:4]=1.Cl.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[CH3:36][C:37]1([CH3:49])[S:41][C@@H:40]2[C@H:42]([NH2:45])[C:43](=[O:44])[N:39]2[C@H:38]1[C:46]([OH:48])=[O:47]>C(Cl)Cl.C(N(CC)CC)C.CC(N(C)C)=O>[CH3:36][C:37]1([CH3:49])[S:41][C@@H:40]2[C@H:42]([NH:45][C:10]([C@H:9]([NH2:13])[C:6]3[CH:7]=[CH:8][C:3]([OH:2])=[CH:4][CH:5]=3)=[O:12])[C:43](=[O:44])[N:39]2[C@H:38]1[C:46]([OH:48])=[O:47]

Participants

Conditions

Temperature: 22.5 °C

Procedure

A suspension of the potassium salt of D(-) p-hydroxy-N(1-methoxycarbonyl-2-propenyl)-alpha-aminophenylacetic acid (3.607 g, 1.19 cmoles), methylene chloride (25 ml), dimethylacetamide (2.5 ml) and TMSO (1.82 ml) was stirred at room temperature (20-25° C.) for 45 minutes. Thereafter triethylamine hydrochloride (1.63 g; 1.19 cmoles) was added and after 15 minutes the result was a translucid solution which was cooled to -20° C. Pivalyl chloride (1.45 ml; 1.2 cmoles) in methylene chloride (1.25 ml) and a drop of triethylamine were added. The reaction mixture was stirred for 60 minutes at a temperature of from -10 to -7° C. Thereafter a solution of 6-APA (1 cmole) prepared according to Example 1 was added under the conditions specified in that Example. Then, in a like manner, 3.25 g of amoxicillin (ratio of 1:1,50 with respect to 6-APA) were obtained.

Workup

temperaturewas cooled to -20° C
stirringThe reaction mixture was stirred for 60 minutes at a temperature of from -10 to -7° C
additionwas added under the conditions

Sources & evidence

ORD record: ord-1d2aa545c82f411d8e368a3f8782a2c5
Source dataset: uspto-grants-1980_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04193918

Reaction notes

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