Hydrochloric Acid → 4-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride

HRID 424127

Reaction equation

HRID 424127 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH2:14][N:13](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:12]3)([OH:8])[CH2:4][CH2:3]1.[ClH:37]>CO>[ClH:37].[ClH:37].[CH2:14]1[C:15]2[C:11](=[CH:10][C:9]([C:5]3([OH:8])[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:17][CH:16]=2)[CH2:12][NH:13]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 592631371-methyl-4-(2-trityl-2,3-dihydro-1H-isoindol-5-yl)-piperidin-4-ol

Product 1

HCID 666725264-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 1-methyl-4-(2-trityl-2,3-dihydro-1H-isoindol-5-yl)-piperidin-4-ol (1.42 g, 3.0 mmol), 5N hydrochloric acid (5 mL) and methanol (10 mL) was placed under nitrogen then heated to reflux for 80 minutes. After cooling, the mixture was concentrated in vacuo to remove methanol, diluted with water and washed with ethyl acetate (×2). The aqueous phase was concentrated to dryness to afford the title compound in quantitative yield as a black solid. 1H NMR (MeOH-d4) 7.62 (1H, s), 7.57 (1H, d), 7.45 (1H, d), 4.64 (2H, s), 4.63 (2H, s), 3.49-3.46 (4H, m), 2.95 (3H, s), 2.40-2.32 (2H, m), 1.97 (2H, dd).

Workup

  1. temperaturethen heated
  2. temperatureto reflux for 80 minutes
  3. temperatureAfter cooling
  4. concentrationthe mixture was concentrated in vacuo
  5. customto remove methanol
  6. additiondiluted with water
  7. washwashed with ethyl acetate (×2)
  8. concentrationThe aqueous phase was concentrated to dryness

Sources & evidence

ORD record
ord-6dbb9038184243ada906d17adeb554c1
Source dataset
uspto-grants-2012_01
Patent number
US08101648B2

Linked notes

Loading…