Aluminium lithium hydride → HCID 42597449, compound

HRID 1958523Notes

Reaction equation

HRID 1958523 reaction equation
C[O:2][C:3]([C:5]1[C:6]([C:25](OC)=[O:26])=[C:7]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[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>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C:7]2[N:8]3[CH2:9][C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=4[CH2:16][C:17]3=[C:5]([CH2:3][OH:2])[C:6]=2[CH2:25][OH:26])=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 68917363HCID 68917363, compound

Product 1

HCID 42597449HCID 42597449, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of the 3-(4-chlorophenyl)-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-dicarboxylic acid dimethyl ester (5.03 g, 15 mmol) in anhydrous dichloromethane (120 mL) was added dropwise into a stirred suspension of LiAlH4 (1.31 g, 34.5 mmol) in anhydrous diethyl ether (50 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 (2.0 mL), 15% aqueous NaOH (2.0 mL), and water (6.0 mL). The mixture was filtered to remove inorganic salt, the solid residue was washed with hot THF (300 mL). The combined filtrate and washings was evaporated in vacuo to dryness and the solid residue was recrystallized from dichloromethane/ether to give [3-(4-chlorophenyl)-2-hydroxymethyl-5,10-dihydro-pyrrolo[1,2-b]isoquinolin-1-yl]methanol (DA-1116), 3.12 g (61.4%); mp 170-171° C.; 1H NMR (DMSO-d6) δ 4.06 (2H, s, CH2), 4.28 (2H, d, J=5.1 Hz, CH2), 4.50 (2H, d, J=5.1 Hz, CH2), 4.55 (1H, t, J=5.1 Hz, exchangeable, OH), 4.57 (1H, t, J=5.1 Hz, exchangeable, OH), 4.98 (2H, s, CH2), 7.18-7.20 (1H, m, ArH), 7.25-7.30 (2H, m, ArH), 7.36-7.40 (1H, m, ArH), 7.49 (2H, d, J=8.5 Hz, 2×ArH), 7.54 (2H, d, J=8.5 Hz, 2×ArH); m/z 339.82 (M+H)+ Anal. Calcld. for C20H18CINO2: C, 70.69; H, 5.34; N, 4.12. Found: C, 70.42; H, 5.29; N, 4.19.

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 (2.0 mL), 15% aqueous NaOH (2.0 mL), and water (6.0 mL)
  4. filtrationThe mixture was filtered
  5. customto remove inorganic salt
  6. washthe solid residue was washed 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-663beb2def4148b8992537d7f654a7ee
Source dataset
uspto-grants-2013_04
Patent number
US08410130B2

Reaction notes

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