Aluminium lithium hydride → (3-(4-chlorophenyl)-6-methyl-6,11-dihydro-5H-indolizino[6,7-b]indole-1,2-diyl)-dimethanol

HRID 2369347Notes

Reaction equation

HRID 2369347 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:24]3[C:11]([CH2:12][C:13]4[C:21]5[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=5[N:15]([CH3:22])[C:14]=4[CH2:23]3)=[C:10]([C:25](OC)=[O:26])[C:9]=2[C:29](OC)=[O:30])=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>ClCCl.C(OCC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:24]3[C:11]([CH2:12][C:13]4[C:21]5[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=5[N:15]([CH3:22])[C:14]=4[CH2:23]3)=[C:10]([CH2:25][OH:26])[C:9]=2[CH2:29][OH:30])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 71574920dimethyl 3-(4-chlorophenyl)-6-methyl-6,11-dihydro-5H-indolizino[6,7-b]indole-1,2-dicarboxylate

Product 1

HCID 71575205(3-(4-chlorophenyl)-6-methyl-6,11-dihydro-5H-indolizino[6,7-b]indole-1,2-diyl)-dimethanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of dimethyl 3-(4-chlorophenyl)-6-methyl-6,11-dihydro-5H-indolizino[6,7-b]indole-1,2-dicarboxylate (3.2 g, 7 mmol) in anhydrous dichloromethane (35 mL) was added dropwise into a stirred suspension of LiAlH4 (0.6 g, 17.8 mmol) in anhydrous diethyl ether (20 mL) at 0 to −5° C. The reaction mixture was further stirred for 15 min after the addition was completed. The excess hydride was destroyed by the sequential addition of water (1 mL), 15% aqueous NaOH (1 mL), and water (1 mL) at 0° C. The mixture was filtered through a pad of Celite and the solid was washed with dichloromethane. The combined filtrate and washings were evaporated to dryness in vacuo. The residue was triturated with ether to give (3-(4-chlorophenyl)-6-methyl-6,11-dihydro-5H-indolizino[6,7-b]indole-1,2-diyl)-dimethanol (BO-1934), 2.2 g (77%); mp 238-239° C. 1H NMR (DMSO-d6) δ 3.62 (3H, s, Me), 4.10 (2H, s, CH2), 4.29 (2H, m, CH2), 4.55 (2H, s, CH2) 4.59 (2H, brs, exchangeable, 2×OH), 5.16 (2H, s, CH2), 7.04-7.08 (1H, m, ArH), 7.14-7.18 (1H, m, ArH), 7.43-7.45 (1H, m, ArH), 7.53-7.59 (5H, m, 5×ArH). Anal. Calcd for (C23H21ClN2O2.0.5H2O): C, 68.74; H, 5.52; N, 6.97. Found: C, 68.72; H, 5.16; N, 6.94.

Workup

  1. additionafter the addition
  2. customThe excess hydride was destroyed by the sequential addition of water (1 mL), 15% aqueous NaOH (1 mL), and water (1 mL) at 0° C
  3. filtrationThe mixture was filtered through a pad of Celite
  4. washthe solid was washed with dichloromethane
  5. customThe combined filtrate and washings were evaporated to dryness in vacuo
  6. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-2b618acc8b6e478c84f459de02ec0dd5
Source dataset
uspto-grants-2014_04
Patent number
US08703951B2

Reaction notes

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