N-(1-benzyloxycarbonyloxy-3,3-dimethylbut-2(R)-yl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester → N-(2,2-dimethyl-1(S)-hydroxymethyl-propyl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid

HRID 566773Notes

Reaction equation

HRID 566773 reaction equation
C([O:8][C:9](=[O:49])[CH2:10][C@@H:11]([N:32]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][N:46]=[CH:45][CH:44]=3)=[CH:39][CH:38]=2)=[CH:33]1)[C:12]([NH:14][C@H:15]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:16][O:17]C(OCC1C=CC=CC=1)=O)=[O:13])C1C=CC=CC=1>CO.CCOC(C)=O.[OH-].[OH-].[Pd+2]>[CH3:29][C:28]([CH3:31])([CH3:30])[C@H:15]([NH:14][C:12](=[O:13])[C@H:11]([N:32]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:44]=[CH:45][N:46]=[CH:47][CH:48]=3)=[CH:39][CH:38]=2)=[CH:33]1)[CH2:10][C:9]([OH:49])=[O:8])[CH2:16][OH:17]

Participants

5

Reactant 1

HCID 54275701N-(1-benzyloxycarbonyloxy-3,3-dimethylbut-2(R)-yl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester

Product 1

HCID 15487948N-(2,2-dimethyl-1(S)-hydroxymethyl-propyl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-(1-benzyloxycarbonyloxy-3,3-dimethylbut-2(R)-yl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester (140 mg, 0.212 mmol) and Pd(OH)2 (60 mg of 20% Pd by content) in MeOH (1 mL) and EtOAc (9 mL) was stirred under H2 atmosphere for 3 hours. The catalyst was filtered onto Celite and rinsed with 10% MeOH/CHCl3 (75 mL). The filtrate was concentrated in vacuo to provide a yellow solid, which was precipitated from hot CHCl3 solution with hexane to firnish 68 mg (95%) of N-[2,2-dimethyl-1(S)-(hydroxymethyl)propyl]-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid as a yellow solid, mp 192-4° C. 1H NMR (CD3OD): δ 8.56 (d, 1H, J=5.9 Hz), 7.78-7.60 (m, 7H), 7.37 (t, 1H, J=1.9 Hz), 6.96 (t, 1H, J=2.5 Hz), 6.54 (t, 1H, J=1.6 Hz), 5.22 (dd, 1H, J=2.5 Hz), 3.83-3.70 (m, 2H), 3.45-3.40 (m, 1H), 3.22 (d, 1H, J=7.5 Hz), 3.02 (dd, 1H, J=7.2, 16.8 Hz), 0.90 (s, 9H). IR (KBr): 3405, 2960, 1718, 1656, 1602, 1560, 1408, 1364, 1203, 922, 818, 783 cm−1. HRFABMS: Calculated for C25H29N3O4Cs (M+Cs+): 568.1212. Found: 568.1189. Anal. Calculated for C25H29N3O4•0.10 CHCl3: C, 67.38; H, 6.55; N, 9.39. Found: C, 67.69, H, 6.90; N, 9.65.

Workup

  1. filtrationThe catalyst was filtered onto Celite
  2. washrinsed with 10% MeOH/CHCl3 (75 mL)
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto provide a yellow solid, which
  5. customwas precipitated from hot CHCl3 solution with hexane to firnish 68 mg (95%) of N-[2,2-dimethyl-1(S)-(hydroxymethyl)propyl]-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid as a yellow solid, mp 192-4° C

Sources & evidence

ORD record
ord-3e456bbd43bc4f5dbd9fb119579e7fe0
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

Loading…