Trifluoroacetic acid → Ceftobiprole

HRID 1633814Notes

Reaction equation

HRID 1633814 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:42]/[O:43]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)/[C:8]([NH:10][C@@H:11]2[C:18](=[O:19])[N:17]3[C@@H:12]2[S:13][CH2:14][C:15](/[CH:23]=[C:24]2/[C:25](=[O:41])[N:26]([C@@H:29]4[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]4)[CH2:27][CH2:28]/2)=[C:16]3[C:20]([OH:22])=[O:21])=[O:9])[N:3]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:42]/[OH:43])/[C:8]([NH:10][C@@H:11]2[C:18](=[O:19])[N:17]3[C@@H:12]2[S:13][CH2:14][C:15](/[CH:23]=[C:24]2/[C:25](=[O:41])[N:26]([C@@H:29]4[CH2:33][CH2:32][NH:31][CH2:30]4)[CH2:27][CH2:28]/2)=[C:16]3[C:20]([OH:22])=[O:21])=[O:9])[N:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 12993648HCID 12993648, compound

Product 1

HCID 135413542CeftobiproleYield 97.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5.2 (large scale): A suspension of 5.785 g of (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-trityloxyimino-acetylamino]-3-[(E)-(R)-1′-tert.-butoxycarbonyl-2-oxo-[1,3′]bipyrrolidinyl-3-ylidene-methyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid and 1.69 ml of triethylsilane in 25 ml of dichloromethane was treated at −15° with 7.21 ml of trifluoroacetic acid and the solution was heated to 30° for 30 min after which time HPLC indicated completion of the reaction. The mixture was evaporated to dryness, the residue was digested with 60 ml of ethyl acetate, the suspension was filtered and the residue dried to give 3.43 g of the crude title compound as a brown solid, containing about 1.4 equivalents of ethylacetate. 1H-NMR (d6-DMSO): 13.9 (s, br., 1H, COOH); 11.94 (s, 1H, OH); 9.50 (d, J=8.4, 1H, NH—C(7)); 8.96 (s, br., 2H, NH2); 8.07 (s, br., 2H, NH2); 7.26 (s, br., 1H, CH—C(3)); 5.88 (dd, J=8.4 and 4.9, 1H, H—C(7)); 5.18 (d, J=4.9, 1H, H—C(6)); 4.64 (m, 1H); 3.87 (s, br., 2H H2C(4)); 3.9-2.7 (m, 8H); 2.2-2.0 (m, 2H).

Workup

  1. temperaturethe solution was heated to 30° for 30 min after which time HPLC
  2. customcompletion of the reaction
  3. customThe mixture was evaporated to dryness
  4. filtrationthe suspension was filtered
  5. customthe residue dried

Sources & evidence

ORD record
ord-eb9d1447ed0240a5bbe9b60f0d3858d5
Source dataset
uspto-grants-2003_01
Patent number
US06504025B2

Reaction notes

Loading…