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

HRID 41471Notes

Reaction equation

HRID 41471 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-8c06295457a14db2b22260699aff02c7
Source dataset
uspto-grants-2013_09
Patent number
US08530469B2

Reaction notes

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