Methanol → 1,3-Dihydro-3-(4-hydroxybutyl)-1-phenyl-3-(4-pyridinylmethyl)-2H-indol-2-one Hydrochloride

HRID 36366Notes

Reaction equation

HRID 36366 reaction equation
[ClH:1].C([O:4][C:5](=O)[CH2:6][CH2:7][CH2:8][C:9]1([CH2:25][C:26]2[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=2)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:10]1=[O:24])C.B.CO>C1COCC1>[ClH:1].[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1([CH2:25][C:26]2[CH:27]=[CH:28][N:29]=[CH:30][CH:31]=2)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:10]1=[O:24]

Participants

5

Reactant 3

HCID 887MethanolHCID 6331BoraneHCID 1924922,3-Dihydro-2-oxo-1-phenyl-3-(4-pyridinylmethyl)-1H-indole-3-butanoic acid ethyl ester

Product 1

HCID 194389731,3-Dihydro-3-(4-hydroxybutyl)-1-phenyl-3-(4-pyridinylmethyl)-2H-indol-2-one Hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 2,3-Dihydro-2-oxo-1-phenyl-3-(4-pyridinylmethyl)-1H-indole-3-butanoic acid ethyl ester hydrochloride (10.0 g, 22.2 mmol) in 50 ml dry THF was treated with excess 1M BH3 -THF and stirred at room temperature for 3 days. The excess borane was decomposed with MeOH, and the mixture was concentrated in vacuo. The residue was digested with 100 ml 1N HCl for 3 hours at 80° C. , and the solution was concentrated. The residue was partitioned between 200 ml EtOAc and 100 ml 5% NaHCO3. The organic phase was washed with water and brine, dried over MgSO4, filtered, treated with 44 ml 1N HCl-Et2O, evaporated in vacuo. The residue was suspended in hot CH3CN and left standing overnight. The resulting crystals were collected by filtration, washed with Et2O, and dried to give the product in 30% (2.72 g) yield; mp 196°-197° C.; IR(nujol): OH @3356 cm-1 ; C=O @1709 cm -1 ; NMR(CDCl3TMS): δ1.13, 1.24 (2m, 2H, CH2 --C--CO), 2.51 (m, 2H, CH2 --CO), 2.1-3.0 (m, 2H, CH2 --C--C--CO), [3.40 (d, 1H, J=12.4 Hz), 3.54 (d, 1H, J=12.5 Hz), CH2 -Pyr], 3.48 (t, 2H, OCH2), [6.5 (m, 1H), 7.2 (m, 2H), 7.4 (m, 6H), Phe+1,2-Phe], [6.99 (d, 2H), 8.49 (d, 2H), 4-Pyr]; mass spec m/e 373(M+1); Anal calcd for C24H24N2O2HCl, MW 408.93: C, 70.49; H, 6.16; N, 6.85. Found: C, 70.44; H, 6.00; N, 6.67.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. waitThe residue was digested with 100 ml 1N HCl for 3 hours at 80° C.
  3. concentrationthe solution was concentrated
  4. customThe residue was partitioned between 200 ml EtOAc and 100 ml 5% NaHCO3
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. additiontreated with 44 ml 1N HCl-Et2O
  9. customevaporated in vacuo
  10. waitleft
  11. waitstanding overnight
  12. filtrationThe resulting crystals were collected by filtration
  13. washwashed with Et2O
  14. customdried
  15. customto give the product in 30% (2.72 g)
  16. customyield

Sources & evidence

ORD record
ord-eaabbfb0a6364fe7a44af7180be48386
Source dataset
uspto-grants-1995_05
Patent number
US05414004

Reaction notes

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