Hydrochloric Acid → 5-(4-Hydroxy-1-methyl-piperidin-4-ylmethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one

HRID 905857Notes

Reaction equation

C([O:3][C:4]([C:6]1[C:10]([CH3:11])=[CH:9][NH:8][C:7]=1[CH2:12][CH2:13][NH:14][CH2:15][C:16]1([OH:23])[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1)=O)C.O.[OH-].[Li+].Cl>O>[OH:23][C:16]1([CH2:15][N:14]2[CH2:13][CH2:12][C:7]3[NH:8][CH:9]=[C:10]([CH3:11])[C:6]=3[C:4]2=[O:3])[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 135 °C

Procedure

A stirred mixture of 2-{2-[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-amino]-ethyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (5.931 g, 18.36 mmol) in glycol (257 ml) was added with lithium hydroxide monohydrate (6.169 g, 147 mmol). The resulting mixture was heated to 135° C. for 4 hours. The mixture was added with cold water (250 ml), adjusted to pH from 14 to 12 with 2N hydrochloric acid in an ice-water bath. The mixture was extracted with a 10 to 1 solvent mixture of dichloromethane and methanol (200 ml×8). The combined organic extracts were concentrated under reduced pressure and the residue was purified by silica gel column chromatography with dichloromethane:methanol:ammonia (600:45:2) as eluents to give 5-(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (11.837 g) as a light brown oil which was used as such.

Workup

extractionThe mixture was extracted with a 10 to 1 solvent mixture of dichloromethane and methanol (200 ml×8)
concentrationThe combined organic extracts were concentrated under reduced pressure
customthe residue was purified by silica gel column chromatography with dichloromethane:methanol:ammonia (600:45:2) as eluents

Sources & evidence

ORD record: ord-497b80f88131498db79e3f8a4067aa9a
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012966B2

Reaction notes

Loading…