1,1'-Carbonyldiimidazole → 6-(1H-Indole-2-carbonyl)-octahydro-pyrrolo[3,4-b]pyridine-1-carboxylic acid tert-butyl ester

HRID 1984303Notes

Reaction equation

HRID 1984303 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH2:35][C@@H:34]2[CH2:38][NH:39][CH2:40][C@H:33]12)=[O:31])([CH3:28])([CH3:27])[CH3:26]>C1COCC1>[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][CH2:35][CH:34]2[CH2:38][N:39]([C:10]([C:2]3[NH:1][C:9]4[C:4]([CH:3]=3)=[CH:5][CH:6]=[CH:7][CH:8]=4)=[O:12])[CH2:40][CH:33]12)=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 72899Indole-2-carboxylic acidHCID 1519436rel-1,1-Dimethylethyl (4aR,7aR)-octahydro-1H-pyrrolo(3,4-b)pyridine-1-carboxylate

Product 1

HCID 690571026-(1H-Indole-2-carbonyl)-octahydro-pyrrolo[3,4-b]pyridine-1-carboxylic acid tert-butyl esterYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of indole-2-carboxylic acid (67.4 mg, 0.42 mmol) in THF (2.8 mL) was added CDI (68.3 mg, 0.42 mmol) and cis-octahydro-pyrrolo[3,4-b]pyridine-1-carboxylic acid tert-butyl ester (100 mg, 0.44 mmol). After 72 h at rt, the mixture was diluted with satd. aq. NaHCO3 and extracted with CH2Cl2 (3×). The combined organic layers were washed with satd. aq. NaCl, dried (Na2SO4), and concentrated to give a yellow liquid, which was purified by FCC (EtOAc/hexanes) to give a yellow solid (50 mg, 44%). 1H NMR (mixture of rotamers; CDCl3): 7.79-7.72 (m, 1H), 7.72-7.64 (m, 1H), 7.49-7.39 (m, 1H), 7.34-7.29 (m, 1H), 7.25-7.19 (m, 1H), 7.17-7.09 (m, 1H), 6.94-6.89 (m, 1H), 6.89-6.85 (m, 1H), 4.20-3.95 (m, 2H), 3.95-3.86 (m, 0.5H), 3.86-3.69 (m, 2H), 3.69-3.59 (m, 0.5H), 2.91-2.71 (m, 1H), 2.40-2.30 (m, 0.4H), 2.30-2.19 (m, 0.6H), 1.89-1.67 (m, 2H), 1.54-1.42 (m, 9H), 1.41-1.21 (m, 2H).

Workup

  1. additionthe mixture was diluted with satd
  2. extractionaq. NaHCO3 and extracted with CH2Cl2 (3×)
  3. washThe combined organic layers were washed with satd
  4. dry with materialaq. NaCl, dried (Na2SO4)
  5. concentrationconcentrated
  6. customto give a yellow liquid, which
  7. customwas purified by FCC (EtOAc/hexanes)

Sources & evidence

ORD record
ord-6c3b73a7bc5b466e9763293028dfd8a5
Source dataset
uspto-grants-2009_06
Patent number
US07544698B2

Reaction notes

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