Potassium Hydroxide → HCID 57003407, compound

HRID 975993Notes

Reaction equation

HRID 975993 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]=[CH:15][C:14]=2[F:19])[N:9]1[C:20](=[O:38])[C@@H:21]([NH:23][C:24](=[O:37])[NH:25][C:26]1[CH:27]=[C:28]([CH2:32][C:33]([O:35]C)=[O:34])[CH:29]=[CH:30][CH:31]=1)[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+]>O.CO.[OH-].[Na+]>[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]=[CH:15][C:14]=2[F:19])[N:9]1[C:20](=[O:38])[C@@H:21]([NH:23][C:24](=[O:37])[NH:25][C:26]1[CH:27]=[C:28]([CH2:32][C:33]([OH:35])=[O:34])[CH:29]=[CH:30][CH:31]=1)[CH3:22])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 67713397HCID 67713397, compound

Product 1

HCID 57003407HCID 57003407, compoundYield 35.1%

Reagents, catalysts & solvents 2

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

Procedure

The operation is carried out in a fashion similar to that described in Example 77, but starting from 0.38 g of methyl 3-{3-{(2S)-1-[(2R,4R)-4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl]-1-oxo-2-propyl}ureido}-phenylacetate in 6 cm3 of a water/methanol (30/70 by volume) mixture and 0.05 g of potassium hydroxide. The crude product is dissolved in 3.5 cm3 of 0.1N aqueous sodium hydroxide solution. The solution thus obtained is washed with 2 times 10 cm3 of ethyl acetate, filtered and brought to a pH of 2 by addition of a 1N aqueous sulphuric acid solution. The product precipitated is separated by filtration, washed with 2 times 5 cm3 of water and dried in air. 0.13 g of 3-{3-{(2S)-1-[(2R,4R)-4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl]-1-oxo-2-propyl}ureido}phenylacetic acid, melting at 110° C., is thus obtained ([α]D20 =+103°±4° (C=0.244%; DMF), [proton NMR (200 MHz, DMSO D6, δ in ppm, J in Hz), 2 rotamers at room temperature, peak coalescence at 120° C., characteristic chemical shifts at 120° C.: 1.05 (d, J=7, 3H, --CH3): 1.55 (s, 9H, --C(CH3)3); 3.25 (dd, J=12.5 and 7, 1H, of S--CH2); 3.52 (dd, J=12.5 and 6, 1H, the other H of S--CH2 --); 3.53 (s, 2H, ArCH2COO); 4.4 (m, 1H, N--COCH--N); 4.86 (dd, J=7 and 6, N--CH--COO); 6.3 (d, J=8, 1H, --NHCO--); 6.83 (s,1H, S--CH--N); 6.89 (bd, J=8, 1H, in position 4 on CO--NH--Ph--); 7.10 to 7.5 (m, 6H, aromatic); 8.0 (bt, J=8.5, 1H, in position 6 on S--CH--Ph--); 8.29 (broad, 1H, ArNHCO--)], [infrared spectrum (KBr), characteristic bands in cm-1 : 3380, 2980, 2935, 2700 to 2250 (broad band), 1735, 1640, 1615, 1595, 1560, 1490, 1460, 1370, 1235, 1155, 760, 705].

Workup

  1. customThe solution thus obtained
  2. washis washed with 2 times 10 cm3 of ethyl acetate
  3. filtrationfiltered
  4. additionbrought to a pH of 2 by addition of a 1N aqueous sulphuric acid solution
  5. customThe product precipitated
  6. customis separated by filtration
  7. washwashed with 2 times 5 cm3 of water
  8. customdried in air

Sources & evidence

ORD record
ord-99647fa08e1e4db4b3c9c5df2027bf0f
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

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