Dimethylformamide dimethyl acetal → 4-[2-(4,5,6,7-tetrahydro-1H-1,3-diazepin-2-yl)ethyl] 1-piperidinecarboxaldehyde dimethylacetal

HRID 364720Notes

Reaction equation

C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.[NH:15]1[CH2:21][CH2:20][CH2:19][CH2:18][N:17]=[C:16]1[CH2:22][CH2:23][CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.CO[Na].[CH3:33][O:34][CH:35]([O:39][CH3:40])N(C)C>CO>[CH3:33][O:34][CH:35]([O:39][CH3:40])[N:27]1[CH2:26][CH2:25][CH:24]([CH2:23][CH2:22][C:16]2[NH:17][CH2:18][CH2:19][CH2:20][CH2:21][N:15]=2)[CH2:29][CH2:28]1

Participants

Conditions

Temperature: 90 °C

Procedure

The dihydrochloride salt of 4-[2-(4,5,6,7-tetrahydro-1H-1,3-diazepin-2-yl)ethyl]piperidine (1.6 g, 5.8 mM) in methanol (12 ml) which contained MeONa (12 mM) and dimethylformamide dimethyl acetal (20 ml) was heated at 90° C. for 8 hrs. The excess of dimethylformamide dimethylacetal was removed in vacuo to give the 4-[2-(4,5,6,7-tetrahydro-1H-1,3-diazepin-2-yl)ethyl] 1-piperidinecarboxaldehyde dimethylacetal. To the mixture of 6-aminopenicillanic acid (1.1 g, 5 mM) and diisopropylethylamine (0.96 ml) in 20 ml dry CHCl3 was added the solution (CHCl3 8 ml:MeOH 1 ml) of above piperidine-carboxaldehyde dimethylacetal at 0° C. The reaction was stirred at 0° C. for 1 hr and then at room temperature for 3 hrs. The solvent was then removed, and water added (30 ml). The aqueous solution, washed with ethylacetate, was acidified to pH 3 with dilute aqueous HCl and purified on Sephadex LH 20 column to yield [2S-(2alpha,5alpha,6beta)]-6-[[[4-[2-(4,5,6,7-tetrahydro-1H-1,3-diazepin-2-yl)ethyl]-1-piperidinyl]methylene]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid hydrochloride (0.85 g, 38% yield)

Workup

customThe excess of dimethylformamide dimethylacetal was removed in vacuo

Sources & evidence

ORD record: ord-07424a00f6c54daf80e95eae4c4bf6e4
Source dataset: uspto-grants-1986_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04605744

Reaction notes

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