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

HRID 2299954Notes

Reaction equation

HRID 2299954 reaction equation
C([O:8][C:9](=[O:32])[CH2:10][C@@H:11]([N:15]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)=[CH:16]1)[C:12]([NH2:14])=[O:13])C1C=CC=CC=1.CCO[C:36]([CH3:38])=[O:37]>CO.[OH-].[OH-].[Pd+2]>[CH3:16][C:17]([CH3:20])([CH3:18])[C@H:38]([NH:14][C:12](=[O:13])[C@H:11]([N:15]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)=[CH:16]1)[CH2:10][C:9]([OH:8])=[O:32])[CH2:36][OH:37]

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 86758715HCID 86758715, compound

Product 1

HCID 15487948N-(2,2-dimethyl-1(S)-hydroxymethyl-propyl)-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acidYield 95%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

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 mgof 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 CHCl3solution with hexane to furnish 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 C25H29N3O4.0.10CHCl3: 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 CHCl3solution with hexane

Sources & evidence

ORD record
ord-5f268e8263024893bae0c195c61a1a55
Source dataset
uspto-grants-2002_12
Patent number
US06495699B2

Reaction notes

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