N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-(biphenyl-4-yI)-1H-pyrrol-1-yl)succinamic acid benzyl ester → N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-(biphenyl-4-yl)-1H-pyrrol-yl)succinamic acid

HRID 2299911Notes

Reaction equation

HRID 2299911 reaction equation
C([O:8][C:9](=[O:42])[CH2:10][C@@H:11]([N:25]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[CH:32][CH:31]=2)=[CH:26]1)[C:12]([NH:14][C@@H:15]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:16][OH:17])=[O:13])C1C=CC=CC=1>CCOC(C)=O.[Pd]>[CH2:18]([C@H:15]([NH:14][C:12](=[O:13])[C@H:11]([N:25]1[CH:29]=[CH:28][C:27]([C:30]2[CH:31]=[CH:32][C:33]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[CH:34][CH:35]=2)=[CH:26]1)[CH2:10][C:9]([OH:42])=[O:8])[CH2:16][OH:17])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 1

HCID 15459663N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-(biphenyl-4-yI)-1H-pyrrol-1-yl)succinamic acid benzyl ester

Product 1

HCID 15459664N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-(biphenyl-4-yl)-1H-pyrrol-yl)succinamic acidYield 83.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 10% Pd/C (wet DeGussa type, 15 mg ) and N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl]succinamic acid benzyl ester (68 mg, 0.12 mmol) in EtOAc (5 mL) was stirred under H2 for 20 hours. The catalyst was filtered onto Celite and rinsed with MeOH. The filtrate was concentrated under reduced pressure to give a yellow oil, which was purified via flash column chromatography with a 1% HOAc/2-5% MeOH/CH2Cl2 stepwise gradient elution to provide 47 mg (82%) of N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl]succinamic acid as a white solid. 1H NMR (CDCl3): δ 7.66-7.48 (m, 3H), 7.42 (t, 2H, J=7.2 Hz), 7.34-7.28 (m, 1H), 7.21-7.12 (m, 2H), 7.04-6.96 (m, 1H), 6.94 (bs, 1H), 6.68 (dd, 1H, J=2.5, 2.5 Hz), 6.55 (dd, 1H, J=1.6, 1.6 Hz), 5.78 (bd, 1H, J=7.5 Hz), 4.90 (t, 1H, J=7.2 Hz), 4.36-4.02 (m, 1H), 3.68 (dd, 1H, J=3.4, 11.2 Hz), 3.50 (dd, 1H, J=5.3, 9.0 Hz), 3.31 (dd, J=5.9, 7.4 Hz), 3.12 (dd, 1H, J=7.2, 17.1 Hz), 2.74 (ddd, 1H, J=6.2, 14.3, 14.3 Hz), 2.68 (ddd, J=8.7, 14.0, 14.3 Hz). IR (film): 3387, 3028, 2931, 1715, 1660, 1532, 1494, 1204, 702, 698 cm−1. HRFABMS: Calculated for C29H28N2O4Cs (M+Cs+): 643.1209. Found: 643.1185. Anal. calculated for C29H28N2O4.0.1 CHCl3.0.35 H2O: C, 71.80; H, 5.96; N, 5.75. Found: C, 71.92; H, 5.87; N, 5.77.

Workup

  1. filtrationThe catalyst was filtered onto Celite
  2. washrinsed with MeOH
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto give a yellow oil, which
  5. customwas purified via flash column chromatography with a 1% HOAc/2-5% MeOH/CH2Cl2 stepwise gradient elution

Sources & evidence

ORD record
ord-5f4654ffc4d746d08936826442c6373c
Source dataset
uspto-grants-2002_12
Patent number
US06495699B2

Reaction notes

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