Aluminium lithium hydride → 5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentan-1-ol

HRID 599929Notes

Reaction equation

HRID 599929 reaction equation
C[O:2][C:3](=O)[CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:16]2[C:10]([CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)=[N:9]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>CCOCC.C(Cl)Cl.CCOCC>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([C:17]2[N:8]([CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][OH:2])[N:9]=[C:10]3[C:16]=2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[CH:19][CH:20]=1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 24872786HCID 24872786, compound

Product 1

HCID 248727875-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentan-1-olYield 12%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21881112Ethyl ether methylene chlorideSolvent

Procedure

5-[3-(4-Chloro-phenyl)-5,6,7,8-tetrahydro-4H-1,2,6-triaza-azulen-2-yl]-pentanoic acid methyl ester (Example 82, 0.009 g) was dissolved in 9:1 Et2O/CH2Cl2 (3 mL) and the solution was added slowly to a stirred suspension of lithium aluminum hydride (2 mg) in 5 mL of anhydrous Et2O. After stirring at RT for 6 h, the reaction was quenched with 2 mL of water. The mixture was treated with 2 mL of 1 N NaOH, followed by another 2 mL of water. The mixture was then filtered through diatomaceous earth. The organic layer was separated, dried over MgSO4, and concentrated. After further drying via vacuum line, the resulting oil was dissolved in 2 mL of 9:1 CH2Cl2/MeOH and treated with 3 mL of 1 N HCl in Et2O. After 4 h, the volatiles were removed in vacuo. The crude oil was purified by preparative TLC (9:1 CH2Cl2/2 M NH3 in MeOH) to afford 0.001 g of the title compound as a colorless oil. MS (ESI): exact mass calculated for C18H24ClN3O, 333.16. found, m/z 334.2 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.54-7.52 (m, 2H), 7.32-7.30 (m, 2H), 3.95 (t, J=7.1 Hz, 2H), 3.44 (t, J=6.6 Hz, 2H), 3.13-3.09 (m, 2H), 3.03-3.00 (m, 2H), 2.98-2.95 (m, 2H), 2.61-2.58 (m, 2H), 1.70-1.64 (m, 2H), 1.40-1.35 (m, 2H), 1.20-1.16 (m, 2H).

Workup

  1. customthe reaction was quenched with 2 mL of water
  2. additionThe mixture was treated with 2 mL of 1 N NaOH
  3. filtrationThe mixture was then filtered through diatomaceous earth
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customAfter further drying via vacuum line
  8. dissolutionthe resulting oil was dissolved in 2 mL of 9:1 CH2Cl2/MeOH
  9. additiontreated with 3 mL of 1 N HCl in Et2O
  10. waitAfter 4 h
  11. customthe volatiles were removed in vacuo
  12. customThe crude oil was purified by preparative TLC (9:1 CH2Cl2/2 M NH3 in MeOH)

Sources & evidence

ORD record
ord-ce95be8900c14fdfbb1f62c40daa70d8
Source dataset
uspto-grants-2011_03
Patent number
US07897771B2

Reaction notes

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