Potassium Bromide → 7-[2-(5-Amino-[1,2,4]thiadiazol-3-yl)-2-trityloxyimino-acetylamino]-3-formyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester

HRID 1633810Notes

Reaction equation

HRID 1633810 reaction equation
CC1(C)N([O])C(C)(C)CCC1.[O-]Cl.[Na+].[CH:15]([O:28][C:29]([C:31]1[N:32]2[CH:35]([S:36][CH2:37][C:38]=1[CH2:39][OH:40])[CH:34]([NH:41][C:42](=[O:71])[C:43]([C:65]1[N:69]=[C:68]([NH2:70])[S:67][N:66]=1)=[N:44][O:45][C:46]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:33]2=[O:72])=[O:30])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[K+].[Br-].C([O-])(O)=O.[Na+]>ClCCl.O>[CH:15]([O:28][C:29]([C:31]1[N:32]2[CH:35]([S:36][CH2:37][C:38]=1[CH:39]=[O:40])[CH:34]([NH:41][C:42](=[O:71])[C:43]([C:65]1[N:69]=[C:68]([NH2:70])[S:67][N:66]=1)=[N:44][O:45][C:46]([C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)([C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[C:33]2=[O:72])=[O:30])([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 5

HCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 2724126Tempo2×HCID 23665760Sodium Hypochlorite2×HCID 764716187-[2-(5-Amino-[1,2,4]thiadiazol-3-yl)-2-trityloxyimino-acetylamino]-3-hydroxymethyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester

Product 1

HCID 731640087-[2-(5-Amino-[1,2,4]thiadiazol-3-yl)-2-trityloxyimino-acetylamino]-3-formyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl esterYield 74.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2.1 (via TEMPO, NaOCl): A suspension of 22.47 g 7-[2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-trityloxyimino-acetylamino]-3-hydroxymethyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester in 110 ml of dichloromethane was treated with a solution of 369 mg of KBr and 958 mg of NaHCO3 in 70 ml of water, the mixture was cooled to 0° C. and treated with a solution of 391 mg of TEMPO (available from Fluka or as described in Synthesis, 1971, p. 190) in 2 ml of dichloromethane. The mixture was treated under vigorous stirring with 29 ml of NaOCl in water (9.93%) over 2 h and stirring was continued for 2 h after which time HPLC indicated completion of the reaction. The reaction mixture was filtered over Celite, the organic layer was washed with brine, treated with MgSO4 and charcoal and filtered. The filtrate was stirred with 25 g of silica for 10 min, filtered and the filtrate was evaporated to dryness to give 16.61 g of the NMR-pure 7-[2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-trityloxyimino-acetylamino]-3-formyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester as a foam. IR (neat): 3432 w (NH2, NH), 1800 m, 1783 m, 1670 m (C═O). 1H-NMR (d6-DMSO): 9.98 (d, J=9.2, 1H, NH); 9.51 (s, 1H, CHO); 8.14 (s, br., 2H, NH2); 7.55-7.25 (m, 25H, H—ar.); 7.10 (s, 1H, CH(Ph)2); 6.30 (dd, J=9.2 and 5.6, 1H, H—C(7)); 5.41 (D, J=5.6, 1H, H—C(6)); 3.93 and 3.49 (each d, J=each 18, 2H, H2C(4)). MS (CI): 807/100, M+H+).

Workup

  1. additionThe mixture was treated
  2. customcompletion of the reaction
  3. filtrationThe reaction mixture was filtered over Celite
  4. washthe organic layer was washed with brine
  5. additiontreated with MgSO4 and charcoal
  6. filtrationfiltered
  7. stirringThe filtrate was stirred with 25 g of silica for 10 min
  8. filtrationfiltered
  9. customthe filtrate was evaporated to dryness

Sources & evidence

ORD record
ord-2803a960c6e34350a89017c3ec981eb6
Source dataset
uspto-grants-2003_01
Patent number
US06504025B2

Reaction notes

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