Potassium Hydroxide → HCID 54194502, compound

HRID 975991Notes

Reaction equation

HRID 975991 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])[CH2:21][NH:22][C:23](=[O:37])[NH:24][C:25]1[CH:26]=[C:27]([CH:34]=[CH:35][CH:36]=1)[CH:28]([OH:33])[C:29]([O:31]C)=[O:30])=[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])[CH2:21][NH:22][C:23](=[O:37])[NH:24][C:25]1[CH:26]=[C:27]([CH:34]=[CH:35][CH:36]=1)[CH:28]([OH:33])[C:29]([OH:31])=[O:30])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 131719909HCID 131719909, compound

Product 1

HCID 54194502HCID 54194502, compoundYield 22%

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 0.70 g of methyl (RS)-3-{3-{2-[(2R,4R)-4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}mandelate in 7 cm3 of a water/methanol (30/70 by volume) mixture and 0.08 g of potassium hydroxide. The crude product (0.45 g) is dissolved in 8.5 cm3 of a 0.1N aqueous sodium hydroxide solution. The solution thus obtained is washed with 2 times 25 cm3 of ethyl acetate, filtered and acidified to a pH of 2 by addition of a 1N aqueous hydrochloric acid solution. The product precipitated is separated by filtration, washed with 2 times 10 cm3 of water and dried in air. 0.15 g of (RS)-3-{3-{2-[(2R,4R)-4-tert-butoxycarbonyl-2-(2-fluorophenyl)-3-thiazolidinyl]-2-oxoethyl}ureido}mandelic acid is thus obtained in the form of a white product, melting at 135° C. [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 110° C.: characteristic chemical shifts at 110° C. 1.55 (s, 9H, --C(CH3)3); 3.32 and 3.53 (2dd, J=12.5 and 6.5, 2H, S--CH2 --); 3.8 (bd, 1H of N--COCH2 --N); 4.08 (d, J=17.5, 1H, the other H of N--COCH2 --N); 5 (m and s, 2H in total respectively N--CH--COO and Ar--CH--); 6.2 (broad, 1H, --NHCO--); 6.54 (s, 1H, S--CH--N); 7.02 (bd, J=7.5, 1H, in position 4 on CO--NH--Ph); 7.1 to 7.5 (m, 6H, aromatic); 7.94 (dd, J=7.5 and 9, 1H, in position 6 on S--CH--Ph--); 8.5 (broad, --CONH--Ar)], [infrared spectrum (KBr), characteristic bands in cm-1 : 3390, 2980, 2930, 2840, 2700 to 2250 (broad band), 1735, 1650, 1610, 1560, 1490, 1455, 1370, 1230, 1150, 1060, 790, 760, 700].

Workup

  1. customThe solution thus obtained
  2. washis washed with 2 times 25 cm3 of ethyl acetate
  3. filtrationfiltered
  4. additionacidified to a pH of 2 by addition of a 1N aqueous hydrochloric acid solution
  5. customThe product precipitated
  6. customis separated by filtration
  7. washwashed with 2 times 10 cm3 of water
  8. customdried in air

Sources & evidence

ORD record
ord-4db54dbfc4374760a62746551b8c509c
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

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