Formic Acid → sodium (3S,5R,6R)-6-formamido-2,2-dimethylpenam-3-carboxylate

HRID 1283083Notes

Reaction equation

HRID 1283083 reaction equation
[NH2:1][C@@H:2]1[C:13](=[O:14])[N:4]2[C@@H:5]([C:10]([OH:12])=[O:11])[C:6]([CH3:9])([CH3:8])[S:7][C@H:3]12.C[Si](C)(C)Cl.C(N(CC)CC)C.[C:27](OC=O)(=[O:29])C.C(O)=O.C(Cl)(=O)C.Cl.C(N(CC)CC)C.C(C(CCCC)C([O-])=O)C.[Na+:58]>O1CCCC1.CCOCC>[CH:27]([NH:1][C@@H:2]1[C:13](=[O:14])[N:4]2[C@@H:5]([C:10]([O-:12])=[O:11])[C:6]([CH3:9])([CH3:8])[S:7][C@H:3]12)=[O:29].[Na+:58]

Participants

11

Reactant 8

HCID 284Formic AcidHCID 6367Acetyl chlorideHCID 6397ChlorotrimethylsilaneHCID 8471Triethylamine3×HCID 110826-Aminopenicillanic acidHCID 11130Triethylamine hydrochlorideHCID 75269Acetic-formic anhydrideHCID 23672331Sodium 2-ethylhexanoate

Product 1

HCID 86733807sodium (3S,5R,6R)-6-formamido-2,2-dimethylpenam-3-carboxylate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A mixture of (3S,5R,6R)-6-amino-2,2-dimethylpenam-3-carboxylic acid (6APA, 2.2056 g., 10.21 mmole), trimethyl chlorosilane (2.615 ml., 20.42 mmole), and triethylamine (2.84 ml., 20.3 mmole) in tetrahydrofuran, (50 ml.) was stirred for 1 hour at +20° to +25° and then cooled to -70°. To this solution at -70° was added a cold (-60 to -70°) solution of formic-acetic anhydride [generated by stirring formic acid (470 mg., 10.2 mmole), acetyl chloride (0.726 ml., 10.2 mmole) and triethylamine (1.42 ml., 10.2 mmole) at -60 to -70° in tetrahydrofuran (40 ml.). The solution contained suspended triethylamine hydrochloride] and triethylamine (1.42 ml., 10.2 mmole). The temperature of the mixture was allowed to rise to +20° over ca. 1 hour and the mixture was then filtered. The filtrate and washings were stirred and a solution of sodium 2ethylhexanoate (2 g., 12 mmole) in tetrahydrofuran (2ml.) and ether (18 ml.) was added. The white precipitate was isolated by filtration, washed with ether and dried to give sodium (3S,5R,6R)-6-formamido-2,2-dimethylpenam-3-carboxylate as a white powder (1.6127 g., 6.06 mmole, 59.4%); m.p. 238° to 242° (dec.); [α]D + 281° (H2O); νmax. 3412 (NH), 1790 (azetidin-2-one), 1677 and 1505 (CONH), 1602 cm.-1 (CO2 -); τ 1.28 (1H, d, J 9 Hz, NH), 1.90 (1H, s, HCO), 4.40 to 4.60 (2H, m, C5 -H and C6 -H), 6.01 (1H,s, C3 -H), 8.42 (3H, s) and 8.50 (3H,s) (C[CH3 ]2). (Found : C, 40.7; H, 4.3; N, 10.3; Na, 8.6; S, 11.7. C9H11N2NaO4S (266.3) requires C, 40.5; H, 4.1; N, 10.5; Na, 8.6; S, 12.0%).

Workup

  1. temperaturecooled to -70°
  2. waitto rise to +20° over ca. 1 hour
  3. filtrationthe mixture was then filtered
  4. stirringThe filtrate and washings were stirred
  5. customThe white precipitate was isolated by filtration
  6. washwashed with ether
  7. customdried

Sources & evidence

ORD record
ord-4a940e761d11445ebdd60171a15f6074
Source dataset
uspto-grants-1976_08
Patent number
US03974150

Reaction notes

Loading…