Aluminium lithium hydride → HCID 42597684, compound

HRID 1958525Notes

Reaction equation

HRID 1958525 reaction equation
C[O:2][C:3]([C:5]1[C:6]([C:26](OC)=[O:27])=[C:7]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[C:20]([F:25])[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>[F:25][C:20]1[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[CH2:26][OH:27])[CH:23]=[CH:22][C:21]=1[F:24]

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 68917540HCID 68917540, compound

Product 1

HCID 42597684HCID 42597684, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of the 3-(3,4-difluorophenyl)-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-dicarboxylic acid dimethyl ester (7.94 g, 20 mmol) in anhydrous dichloromethane (180 mL) was added dropwise into a stirred suspension of LiAlH4 (1.75 g, 46 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 (2.5 mL), 15% aqueous NaOH (2.5 mL), and water (9.0 mL) at 0° C. The reaction mixture was filtered and the solid residue was washed with hot THF (300 mL). The combined filtrate and washings was evaporated to dryness in vacuo to dryness and the solid residue was recrystallized from dichloromethane/ether to give [3-(3,4-difluorophenyl)-2-hydroxymethyl-5,10-dihydropyrrolo[1,2-b]isoquinolin-1-yl]methanol (DA-1112), 4.57 g (67%); mp 145-146° 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), 4.62 (1H, t, J=5.1 Hz, exchangeable, OH), 5.02 (2H, s, CH2), 7.17-7.22 (1H, m, ArH), 7.24-7.35 (3H, m, 3×ArH), 7.34-7.36 (1H, m, ArH), 7.50-7.58 (2H, m, ArH) m/z 341.00 (M+H)+ Anal. Calcld. for C20H17F2NO2: C, 70.37; H, 5.02; N, 4.10. Found: C, 70.31; H, 4.91; 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 (2.5 mL), 15% aqueous NaOH (2.5 mL), and water (9.0 mL) at 0° C
  4. filtrationThe reaction mixture was filtered
  5. washthe solid residue was washed with hot THF (300 mL)
  6. customThe combined filtrate and washings was evaporated to dryness in vacuo to dryness
  7. customthe solid residue was recrystallized from dichloromethane/ether

Sources & evidence

ORD record
ord-7b290c9d66214397a6b9d02862de5adb
Source dataset
uspto-grants-2013_04
Patent number
US08410130B2

Reaction notes

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