Potassium Hydroxide → HCID 10052288, compound

HRID 975989Notes

Reaction equation

HRID 975989 reaction equation
[OH-].[K+].[C:3]([O:7][C:8]([C@@H:10]1[CH2:14][S:13][C@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[N:11]1[C:22](=[O:39])[CH2:23][NH:24][C:25](=[O:38])[NH:26][C:27]1[CH:28]=[C:29]([CH2:33][C:34]([O:36]C)=[O:35])[CH:30]=[CH:31][CH:32]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>O.CO.O.[OH-].[Na+]>[C:3]([O:7][C:8]([C@@H:10]1[CH2:14][S:13][C@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[N:11]1[C:22](=[O:39])[CH2:23][NH:24][C:25](=[O:38])[NH:26][C:27]1[CH:28]=[C:29]([CH2:33][C:34]([OH:36])=[O:35])[CH:30]=[CH:31][CH:32]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 2

HCID 14797Potassium HydroxideHCID 53679518HCID 53679518, compound

Product 1

HCID 10052288HCID 10052288, compoundYield 28.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 14798Sodium HydroxideSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
25 °C

Procedure

At a temperature in the vicinity of 25° C., 0.12 g of potassium hydroxide is added to a solution of 0.95 g of methyl (2R,4R)-3-{3-{2-[4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}phenylacetate in 6 cm3 of a water/methanol (30/70 by volume) mixture. The reaction mixture is stirred for 3 hours at a temperature in the vicinity of 25° C. then concentrated to about half under reduced pressure. The solution obtained is diluted with 40 cm3 of water, washed with 2 times 30 cm3 of ethyl ether, then brought to a pH of 2 by addition of 2.1 cm3 of a 1N aqueous sulphuric acid solution. The insoluble product is separated by filtration and 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. The amorphous product thus obtained (0.26 g) is dissolved in a 1N aqueous sodium hydroxide solution. This solution is filtered, then acidified by addition of a 1N aqueous sulphuric acid solution. The product thus precipitated is separated by filtration, washed with 3 times 10 cm3 of water, then dried in air. 0.26 g of (2R,4R)-3-{3-{2-[4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}phenylacetic acid, melting at 110° C., is thus obtained ([α]D20 =+51.1°±1.6° (C=0.528%; DMF), [proton NMR (200 MHz, DMSO D6 plus several drops of CD3COOD, δ in ppm, J in Hz), 2 rotamers at room temperature, peak coalescence at 120° C., characteristic chemical shifts at 120° C.: 1.55 (s, 9H, --C(CH3)3); 3.34 and 3.52 (2dd, J=12.5 and 6.5, 2H, S--CH2 --); 3.51 (s, 2H, ArCH2COO--); 3.8 and 4.07 (2d, J=17.5, 2H, N--COCH2 --N); 5.02 (t, J=6.5, N--CH--COO); 6.55 (s, 1H, S--CH--N); 6.85 (bd, J=8, 1H, in position 4 on CO--NH--Ph); 7.05 to 7.4 (m, 6H, aromatic); 7.93 (bt, J=8.5, 1H, in position 6 on S--CH--Ph--)], [infrared spectrum (KBr), characteristic bands in cm-1 : 3380, 2980, 2930, 2700 to 2250 (broad band), 1735, 1610, 1615, 1595, 1560, 1490, 1460, 1370, 1230, 1155, 760, 705].

Workup

  1. concentrationthen concentrated to about half under reduced pressure
  2. customThe solution obtained
  3. washwashed with 2 times 30 cm3 of ethyl ether
  4. additionbrought to a pH of 2 by addition of 2.1 cm3 of a 1N aqueous sulphuric acid solution
  5. customThe insoluble product is separated by filtration
  6. custompurified by chromatography on silica [eluent: ethyl acetate/methanol (90/10 by volume)]
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated to dryness under reduced pressure at 40° C
  9. customThe amorphous product thus obtained (0.26 g)
  10. filtrationThis solution is filtered
  11. additionacidified by addition of a 1N aqueous sulphuric acid solution
  12. customThe product thus precipitated
  13. customis separated by filtration
  14. washwashed with 3 times 10 cm3 of water
  15. customdried in air

Sources & evidence

ORD record
ord-1fda6e3ff07a446da79417c97e5a8a24
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

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