Phosphorus pentachloride → 7-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

HRID 1995794Notes

Reaction equation

HRID 1995794 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[C:7]([O:11][C:12]([CH2:14][O:15][N:16]=[C:17]([C:21]1[N:25]=[C:24]([NH2:26])[S:23][N:22]=1)[C:18]([OH:20])=O)=[O:13])([CH3:10])([CH3:9])[CH3:8].[NH2:27][CH:28]1[C:48](=[O:49])[N:30]2[C:31]([C:45]([OH:47])=[O:46])=[C:32]([CH2:35][S:36][C:37]3[N:41]([CH2:42][C:43]#[CH:44])[N:40]=[N:39][N:38]=3)[CH2:33][S:34][C@H:29]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:7]([O:11][C:12]([CH2:14][O:15][N:16]=[C:17]([C:21]1[N:25]=[C:24]([NH2:26])[S:23][N:22]=1)[C:18]([NH:27][CH:28]1[C:48](=[O:49])[N:30]2[C:31]([C:45]([OH:47])=[O:46])=[C:32]([CH2:35][S:36][C:37]3[N:41]([CH2:42][C:43]#[CH:44])[N:40]=[N:39][N:38]=3)[CH2:33][S:34][C@H:29]12)=[O:20])=[O:13])([CH3:8])([CH3:9])[CH3:10]

Participants

7

Reactant 5

HCID 24819Phosphorus pentachlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 130511567-amino-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acidHCID 545194092-Tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetic acid

Product 1

HCID 1317130887-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acidYield 59.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a solution of phosphorus pentachloride (2.50 g) in methylene chloride (60 ml) was added 2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetic acid (syn isomer)(3.02 g) at -15° C. and the mixture was stirred for 45 minutes at -10° to -13° C. On the other hand, a mixture of 7-amino-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (3.52 g) and trimethylsilylacetamide (10 g) in methylene chloride (50 ml) was warmed to make a clear solution and then cooled to -10° C. The solution was added to the above activated mixture at a time and the mixture was stirred for 15 minutes at -5° to 10° C. The reaction mixture was poured into an aqueous solution (120 ml) of sodium bicarbonate (6.7 g) and stirred for 30 minutes at room temperature. The aqueous layer was separated and ethyl acetate was added thereto. The resulting mixture was adjusted to pH 3 with 6 N hydrochloric acid. The ethyl acetate layer was separated, dried over magnesium sulfate and then evaporated. The residue was pulverized with isopropyl ether and then dried to give 7-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer)(3.8 g), mp. 120° to 125° C. (dec.).

Workup

  1. temperaturewas warmed
  2. additionThe solution was added to the above activated mixture at a time
  3. stirringthe mixture was stirred for 15 minutes at -5° to 10° C
  4. stirringstirred for 30 minutes at room temperature
  5. customThe aqueous layer was separated
  6. additionethyl acetate was added
  7. customThe ethyl acetate layer was separated
  8. dry with materialdried over magnesium sulfate
  9. customevaporated
  10. customdried

Sources & evidence

ORD record
ord-4d1e654a1d444b8a9ea20715943f635c
Source dataset
uspto-grants-1983_09
Patent number
US04405617

Reaction notes

Loading…