HCID 53665158, compound → HCID 54257773, compound

HRID 975963Notes

Reaction equation

HRID 975963 reaction equation
[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][S:11][C@H:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)[N:9]1[C:20](=[O:41])[CH2:21][NH:22][C:23](=[O:40])[NH:24][C:25]1[CH:26]=[C:27]([CH:37]=[CH:38][CH:39]=1)[C:28]([O:30]CC[Si](C)(C)C)=[O:29])=[O:7])([CH3:4])([CH3:3])[CH3:2]>[F-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][S:11][C@H:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=2)[N:9]1[C:20](=[O:41])[CH2:21][NH:22][C:23](=[O:40])[NH:24][C:25]1[CH:26]=[C:27]([CH:37]=[CH:38][CH:39]=1)[C:28]([OH:30])=[O:29])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 1

HCID 53665158HCID 53665158, compound

Product 1

HCID 54257773HCID 54257773, compoundYield 16.5%

Reagents, catalysts & solvents 1

HCID 2724141Tetrabutylammonium FluorideSolvent

Procedure

The operation is carried out in a fashion similar to that described in Example 41, but starting from 1.6 g of 2-trimethylsilylethyl (2R,4R)-3-{3-{2-[4-tert-butoxycarbonyl-2-(3-fluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}benzoate in 5.3 cm3 of 1M tetrabutylammonium fluoride solution. The crude product is purified by chromatography on silica [eluent: ethyl acetate/methanol (90/10 by volume)]. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure at 40° C. After vigorous stirring in diisopropyl ether, 0.22 g of (2R,4R)-3-{3-{2-[4-tert-butoxycarbonyl-2-(3-fluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}benzoic acid is thus obtained in the form of an amorphous solid ([α]D20 =+79.0°±2.0° (C=0.43%; CHCl3)) [proton NMR (250 MHz, DMSO D6, δ in ppm), 2 rotamers at room temperature, characteristic chemical shifts at 25° C.: 1.5 (bs, 9H, (CH3)3); 7.1 to 7.6 (m, 7H, aromatic); 8.0 (bs, 1H, N--C6H4 -- in position 2). Infrared spectrum (KBr), characteristic bands in cm-1 : 3380, 2975, 2930, 2600, 1715, 1695, 1650, 1610, 1590, 1560, 1490, 1450, 1370, 1240, 1150, 780, 755, 685].

Workup

  1. customThe crude product is purified by chromatography on silica [eluent: ethyl acetate/methanol (90/10 by volume)]
  2. additionThe fractions containing the expected product
  3. concentrationconcentrated to dryness under reduced pressure at 40° C

Sources & evidence

ORD record
ord-5dd01fee1ad74d6cbfa7db7bc034406e
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

Loading…