Indole → HCID 57031743, compound

HRID 975986Notes

Reaction equation

HRID 975986 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH2:11][CH2:10][C@H:9]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C2C(=CC=CC=2)C=C1.C(OC(N1C(OC)CC[C@H]1C(OC(C)(C)C)=O)=O)(C)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH2:11][CH2:10][C@H:9]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:1]([O:5][C:6]([N:8]1[C@H:12]([C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)[CH2:11][CH2:10][C@H:9]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 798IndoleHCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 10424951HCID 10424951, compoundHCID 57233414HCID 57233414, compound

Product 2

HCID 57031743HCID 57031743, compoundHCID 57233414HCID 57233414, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

tert-Butyl (2S,5R)-1-tert-butoxycarbonyl-5-(3-indolyl)-2-pyrrolidinecarboxylate may be prepared as follows: a solution of 3.5 g of indole in 30 cm3 of methylene chloride is added to a solution of 10.0 g of tert-butyl (2S,5RS)-1-tert-butyoxycarbonyl-5-methoxy-2-pyrrolidinecarboxylate and 0.6 g of para-toluenesulphonic acid in 100 cm3 of anhydrous methylene chloride, cooled to a temperature in the vicinity of 5° C. At the end of the addition, the reaction mixture is brought to a temperature in the vicinity of 25° C., stirred for 2 hours at that temperature, then hydrolysed by addition of 40 cm3 of a saturated aqueous sodium bicarbonate solution. The organic phase is decanted and the aqueous phase is extracted with 2 times 50 cm3 of methylene chloride. The organic phases are combined, dried over magnesium sulphate and concentrated to dryness under reduced pressure at 30° C. The residue obtained is purified by chromatography on silica [eluent: ethyl acetate/cyclohexane (10/90 by volume)]. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure at 35° C. After vigorous stirring in diisopropyl ether, 1.2 g of tert-butyl (2S,5R)-1-tert-butoxycarbonyl-5-(3-indolyl)-2-pyrrolidinecarboxylate (first elution product), melting at 214° C. and 0.8 g of tert-butyl (2S,5S)-1-tert-butoxycarbonyl-5-(3-indolyl)-2-pyrrolidinecarboxylate (second elution product), melting at 194° C., are thus obtained.

Workup

  1. additionAt the end of the addition
  2. customis brought to a temperature in the vicinity of 25° C.
  3. customThe organic phase is decanted
  4. extractionthe aqueous phase is extracted with 2 times 50 cm3 of methylene chloride
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure at 30° C
  7. customThe residue obtained
  8. customis purified by chromatography on silica [eluent: ethyl acetate/cyclohexane (10/90 by volume)]
  9. additionThe fractions containing the expected product
  10. concentrationconcentrated to dryness under reduced pressure at 35° C
  11. stirringAfter vigorous stirring in diisopropyl ether

Sources & evidence

ORD record
ord-276e3f428ca04340a0edf79910b2eac0
Source dataset
uspto-grants-1997_03
Patent number
US05610144

Reaction notes

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