Potassium Hydroxide → HCID 9810015, compound

HRID 861850Notes

Reaction equation

HRID 861850 reaction equation
C[O:2][C:3]([CH2:5][C:6]1[CH:7]=[C:8]([NH:12][C:13](=[O:47])[NH:14][CH2:15][C:16]([N:18]2[CH:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[CH:21]([S:30]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[CH2:20][CH:19]2[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[O:17])[CH:9]=[CH:10][CH:11]=1)=[O:4].[OH-].[K+]>CO.O>[C:43]([O:42][C:40]([CH:19]1[CH2:20][CH:21]([S:30]([C:33]2[CH:34]=[CH:35][C:36]([Cl:39])=[CH:37][CH:38]=2)(=[O:32])=[O:31])[CH:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[F:29])[N:18]1[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:47])[NH:12][C:8]1[CH:7]=[C:6]([CH2:5][C:3]([OH:4])=[O:2])[CH:11]=[CH:10][CH:9]=1)=[O:41])([CH3:46])([CH3:44])[CH3:45]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 86752032HCID 86752032, compound

Product 1

HCID 9810015HCID 9810015, compoundYield 38.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

A To a solution of 2.5 g of tert-butyl (2RS,4SR,5RS)-1-{2-[3-(3-methoxycarbonylmethylphenyl)ureido]acetyl}-5-(2-fluorophenyl)-4-(4-chlorophenyl)sulphonyl-2-pyrrolidinecarboxylate in 60 cm3 of methanol and 30 cm3 of distilled water is added, at a temperature in the region of 20° C., 0.2 g of potassium hydroxide. The reaction mixture is stirred for twenty hours at a temperature in the region of 20° C., and then concentrated under reduced pressure. The residue is taken up in 100 cm3 of distilled water, washed with three times 75 cm3 of diethyl ether, acidified to a pH in the region of 1 by aqueous normal hydrochloric acid and extracted with three times 75 cm3 of ethyl acetate. The extracts are combined, washed with three times 50 cm3 of saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The residue is purified by chromatography on 80 g of silica contained in a column 3.2 cm in diameter [eluent: dichloromethane/methanol (95/5 by volume)]. The fractions containing the expected product are combined and concentrated under reduced pressure. 0.95 g of (2RS,4SR,5RS)-3-(3-{2-[2-tert-butoxycarbonyl-5-(2-fluorophenyl)-4-(4-chlorophenyl)sulphonyl-1-pyrrolidinyl]-2-oxoethyl}ureido)phenylacetic acid is thus obtained [Rf=0.5; eluent: methylene chloride/methanol (90/10); 1H NMR spectrum (250 MHz, (CH3)2SO with addition of a few drops of CD3COOD, at a temperature of 393 K, δ in ppm): 1.54 (s, 9H: C(CH3)3); from 2.40 to 2.60 and 2.85 (2 mts, 1H each: CH2 at 3); 3.50 (s, 2H: ArCH2COO); 3.70 and 3.97 (broad d and d respectively, J=17 Hz, 1H each: COCH2N); 4.09 (mt, 1H: H4); 4.68 (t, J=8 Hz, 1H: H2); 5.73 (d, J=3 Hz, 1H: H5); 6.86 (broad d, J=7.5 Hz, 1H: aromatic H (H4: ortho to the CH2)); from 7.00 to 7.40 (mt, 6H: aromatic H); 7.68 (broad d, J=8.5 Hz, 2H: H of the aromatic at 4 (H ortho to the Cl)); 7.82 (broad t, J=8 Hz, 1H: H of the aromatic at 5 (H6)); 7.96 (broad d, J=8.5 Hz, 2H: aromatic H at 4 (H meta to the Cl))].

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed with three times 75 cm3 of diethyl ether
  3. extractionextracted with three times 75 cm3 of ethyl acetate
  4. washwashed with three times 50 cm3 of saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by chromatography on 80 g of silica
  8. additionThe fractions containing the expected product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b2b7ba54bd7548c9bc97c99b9c36f887
Source dataset
uspto-grants-1998_02
Patent number
US05716936

Reaction notes

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