Pyrrolo(1,2-b)isoquinoline-1,2-dicarboxylic acid, 5,10-dihydro-3-methyl-, dimethyl ester → (2-Hydroxymethyl-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinolin-1-yl)methanol

HRID 1958521Notes

Reaction equation

HRID 1958521 reaction equation
C[O:2][C:3]([C:5]1[C:6]([C:19](OC)=[O:20])=[C:7]([CH3:18])[N:8]2[C:17]=1[CH2:16][C:15]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:9]2)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>ClCCl.C(OCC)C>[OH:20][CH2:19][C:6]1[C:5]([CH2:3][OH:2])=[C:17]2[CH2:16][C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[CH2:9][N:8]2[C:7]=1[CH3:18]

Participants

5

Reactant 2

HCID 461168Pyrrolo(1,2-b)isoquinoline-1,2-dicarboxylic acid, 5,10-dihydro-3-methyl-, dimethyl esterHCID 21226445Aluminium lithium hydride

Product 1

HCID 42597446(2-Hydroxymethyl-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinolin-1-yl)methanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-methyl-5,10-dihydropyrrolo[1,2-b]-isoquinoline-1,2-dicarboxylic acid dimethyl ester (2.39 g, 8 mmol) in anhydrous dichloromethane (20 mL) was added dropwise into a stirred suspension of LiAlH4 (0.69 g, 18.4 mmol) in anhydrous diethyl ether (30 mL) at 10-15° C. The reaction mixture was further stirred for 2 hours after the addition was completed. The mixture was cooled in an ice bath and the excess hydride was destroyed by the sequential addition of water (1.2 mL), 15% aqueous NaOH (1.2 mL), and water (3.6 mL) at 0° C. The mixture was filtered, and the inorganic solid was removed by filtration, washed with hot THF (300 mL). The combined filtrate and washings was evaporated in vacuo to dryness. The solid residue was recrystallized from dichloromethane/ether to give (2-hydroxymethyl-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinolin-1-yl)methanol (DA-1107), 1.47 g (76.2%); mp 99-101° C.; 1H NMR (DMSO-d6) δ 2.22 (3H, s, Me), 3.96 (2H, s, CH2), 4.34 and 4.39 (each 3H, brs, CH2 and exchangeable, OH), 4.93 (2H, s, CH2), 7.26 and 7.34 (each 2H, brs, 4×ArH); m/z 243.0 (M+H)+ Anal. Calcld. for C15H17NO2.0.1H2O): C, 73.50; H, 7.07; N, 5.71. Found: C, 73.42; H, 6.97; N, 5.71.

Workup

  1. additionafter the addition
  2. temperatureThe mixture was cooled in an ice bath
  3. customthe excess hydride was destroyed by the sequential addition of water (1.2 mL), 15% aqueous NaOH (1.2 mL), and water (3.6 mL) at 0° C
  4. filtrationThe mixture was filtered
  5. customthe inorganic solid was removed by filtration
  6. washwashed with hot THF (300 mL)
  7. customThe combined filtrate and washings was evaporated in vacuo to dryness
  8. customThe solid residue was recrystallized from dichloromethane/ether

Sources & evidence

ORD record
ord-3c6276f6c7eb4578bfca364e75fb6260
Source dataset
uspto-grants-2013_04
Patent number
US08410130B2

Reaction notes

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