Sodium Hydroxide → HCID 9960455, compound

HRID 1266452Notes

Reaction equation

HRID 1266452 reaction equation
C([O:3][C:4]([CH:6]1[CH:10]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:39])[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:36])=[O:28])=[C:22]([O:37][CH3:38])[CH:21]=3)=[CH:13][CH:12]=2)[CH2:9][N:8]([C:40](=[O:47])[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:7]1)=[O:5])C.[OH-].[Na+]>C(O)C>[C:40]([N:8]1[CH2:9][CH:10]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:39])[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:36])=[O:28])=[C:22]([O:37][CH3:38])[CH:21]=3)=[CH:13][CH:12]=2)[CH:6]([C:4]([OH:5])=[O:3])[CH2:7]1)(=[O:47])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 69832616HCID 69832616, compound

Product 1

HCID 9960455HCID 9960455, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
10 °C

Procedure

A stirred solution of 1-benzoyl-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester (5 g, Reference Example 7) in ethanol (60 ml), at 23° C., was treated dropwise with sodium hydroxide solution (16 ml, 1N). After stirring for 24 hours the mixture was evaporated (40° C. and 2.7 kPa) and the residue was treated with water (300 ml). The mixture was cooled to 10° C, then treated with hydrochloric acid (25 ml, 1N) and then stood at 23° C. for 20 hours. The resulting white precipitate was filtered, then dried under reduced pressure (40° C. and 2.7 kPa) for 45 minutes and then recrystallised from aqueous ethanol (40 ml) affording the title compound (3.25 g) as a white crystalline powder, m.p. 248° C. TLC: RF=45/78 (on silica eluting with a mixture of dichloromethane and methanol, 90:10). 1H-NMR [500 MHz, (CD3)2SO at 373°K.]: δ 2.29 (s, 3H); 3.26 (m, 1H); 3.50 to 3.65 (m, 2H); 3.61 (s, 2H); 3.76 (m, 1H);3.85 to 4.00 (m, 2H); 3.91 (s, 3H); 6.88 (d, J=8 Hz, 1H); 6.99 (t, J=7.5 Hz, 1H); 7.03 (bs, 1H); 7.14 (t, J=7.5 Hz, 1H); 7.18 (d, J=7.5 Hz, 1H); 7.26 (d, J=8.5 Hz, 2H); 7.45 (m, 3H); 7.55 (m, 4H); 7.70 (d, J=7.5 Hz, 1H); 8.01 (d, J=8 Hz, 1H); 8.10 (bs, 1H); 8.26 (bs, 1H); 9.64 (bs, 1H); 11.50 to 12.30 (b, 1H). MS [FAB (meta-nitrobenzylalcohol)]: 607 [M+H]+.

Workup

  1. customwas evaporated (40° C. and 2.7 kPa)
  2. additionthe residue was treated with water (300 ml)
  3. additiontreated with hydrochloric acid (25 ml, 1N)
  4. waitstood at 23° C. for 20 hours
  5. filtrationThe resulting white precipitate was filtered
  6. customdried under reduced pressure (40° C. and 2.7 kPa) for 45 minutes
  7. customrecrystallised from aqueous ethanol (40 ml)

Sources & evidence

ORD record
ord-81f2a2ce3ce2493e97339960cae2a1e0
Source dataset
uspto-grants-2003_04
Patent number
US06548533B2

Reaction notes

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