Dicyclohexylcarbodiimide → HCID 131710403, compound

HRID 258652Notes

Reaction equation

HRID 258652 reaction equation
[C:1]([O:5][N:6]=[C:7]([C:11]1[C:12]2[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=2[S:14][CH:15]=1)[C:8]([OH:10])=O)([CH3:4])([CH3:3])[CH3:2].[NH2:20][C@@H:21]1[C:52](=[O:53])[N:23]2[C:24]([C:36]([O:38]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:37])=[C:25]([CH2:28][S:29][C:30]3[S:31][C:32]([CH3:35])=[N:33][N:34]=3)[CH2:26][S:27][C@H:22]12.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CN(C)C=O>[C:1]([O:5][N:6]=[C:7]([C:11]1[C:12]2[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=2[S:14][CH:15]=1)[C:8]([NH:20][C@@H:21]1[C:52](=[O:53])[N:23]2[C:24]([C:36]([OH:38])=[O:37])=[C:25]([CH2:28][S:29][C:30]3[S:31][C:32]([CH3:35])=[N:33][N:34]=3)[CH2:26][S:27][C@H:22]12)=[O:10])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 10255782HCID 10255782, compoundHCID 53873735HCID 53873735, compound

Product 1

HCID 131710403HCID 131710403, compoundYield 139.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 2-(t-butoxyimino)-2-(benzo-[b]-thien-3-yl)-acetic acid (1.11 g) in methylene chloride (5 ml.) and dimethylformamide (1 ml) was added to a solution of diphenylmethyl 7β-amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethylceph-3-em-4-carboxylate (2.04 g) in methylene chloride (20 ml.). A solution of dicyclohexylcarbodiimide (0.823 g) in methylene chloride (5 ml) was added to the above stirred solution at 20°. The mixture was kept at 5° for 16 hours and was then filtered. The filtrate was washed with 2 N hydrochloric acid, dilute sodium bicarbonate solution, water and brine, dried (MgSO4) and concentrated under reduced pressure to give the crude diphenylmethyl ester of the title compound as an orange foam (3.37 g.). The foam was dissolved in anisole (6 ml) and the solution was treated with trifluoroacetic acid (25 ml.). After 5 minutes at 20° the solution was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the resulting solution was again concentrated. The residue was then partitioned between ethyl acetate and dilute sodium bicarbonate solution. The ethyl acetate layer was thoroughly extracted with dilute sodium bicarbonate solution and the combined extracts were washed with ethyl acetate and then were covered with ethyl acetate and taken to pH 2 with concentrated hydrochloric acid. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined ethyl acetate extracts were washed with water and brine, dried and concentrated under reduced pressure to a low volume. The solution was then added dropwise to stirred petroleum (bp. 40°-60°, 400 ml) and the precipitate was collected and washed with petroleum to give the title acid as a buff solid (1.0 g, 41%), [α]D -87°(c 1 in DMSO) λmax. (pH 6 phosphate buffer) 277.5 nm (ε 16,850) νmax. (Nujol) include 1786 (β-lactam), 1672 and 1520 cm.-1 (CONH) τ values (DMSO-d6) include 0.27 (d, J 8 Hz; NH), 1.38 (m; H-4 benzo-[b]-thienyl) 1.86 (m; benzo-[b]-thienyl H-7), 2.15 (s; benzo-[b]-thienyl H-2) 2.44 (m; benzo-[b]-thienyl H-5 and H-6), 4.05 (dd, J 8 and 5 Hz; H-7), 4.72 (d, J 5 Hz; H-6) 5.40+ 5.74 (2ds, J 13 Hz; C-3 CH2), 6.13+ 6.37 (2 ds, J 18 Hz; C-2 CH2), 7.29 (s; CH3) and 8.57 (s; C(CH3)3).

Workup

  1. filtrationwas then filtered
  2. washThe filtrate was washed with 2 N hydrochloric acid, dilute sodium bicarbonate solution, water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f8e3eb471a9e4a7c9f3f939395649609
Source dataset
uspto-grants-1977_07
Patent number
US04033950

Reaction notes

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