Aluminium lithium hydride → 4-[4-(6-Fluoro-benzo[b]thiophen-3-yl)-[1,4]diazapan-1-yl]butylamine

HRID 1986908Notes

Reaction equation

HRID 1986908 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:9]=[CH:10][C:11]2[C:15]([N:16]3[CH2:22][CH2:21][CH2:20][N:19]([CH2:23][CH2:24][CH2:25][C:26]#[N:27])[CH2:18][CH2:17]3)=[CH:14][S:13][C:12]=2[CH:28]=1>C(OCC)C>[F:7][C:8]1[CH:9]=[CH:10][C:11]2[C:15]([N:16]3[CH2:22][CH2:21][CH2:20][N:19]([CH2:23][CH2:24][CH2:25][CH2:26][NH2:27])[CH2:18][CH2:17]3)=[CH:14][S:13][C:12]=2[CH:28]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 577225594-[4-(6-Fluoro-benzo[b]thiophen-3yl)-[1,4]diazapan-1-yl]butyronitrile

Product 1

HCID 577225964-[4-(6-Fluoro-benzo[b]thiophen-3-yl)-[1,4]diazapan-1-yl]butylamineYield 76.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

Add over 30 min, at room temperature, a solution of LiAlH4 in diethyl ether (1M, 72.5 mL) to a solution of 4-[4-(6-fluoro-benzo[b]thiophen-3-yl)-[1,4]diazapan-1-yl]butyronitrile (Example 5) (11.5 g, 36.2 mmol) in dry diethyl ether (200 mL). Heat the solution to reflux for 5 h. After that time, allow the solution to cool to room temperature and carefully quench the reaction with water and aqueous sodium hydroxide solution. Separate the phases, and re-extract the aqueous phase with EtOAc. Dry the combined organic phases over MgSO4 and remove the solvent under vacuum. Purify the crude product by column chromatography (CH2Cl2/MeOH/NH4OH 9:2:0.25) to obtain 8.9 g of a colorless oil LC/MS, (LiChrospher 5μ, RP-18, 250 mm CH3CN/Water(0.05% TFA)-gradient 2%→98% (20 min), Flow: 0.75 mL/min), tR=7.79 min, m/z=321.3.

Workup

  1. additionAdd over 30 min, at room temperature
  2. temperatureHeat the solution
  3. temperatureto reflux for 5 h
  4. customcarefully quench
  5. customthe reaction with water and aqueous sodium hydroxide solution
  6. customSeparate the phases
  7. extractionre-extract the aqueous phase with EtOAc
  8. dry with materialDry the combined organic phases over MgSO4
  9. customremove the solvent under vacuum
  10. customPurify the crude product by column chromatography (CH2Cl2/MeOH/NH4OH 9:2:0.25)

Sources & evidence

ORD record
ord-fb6c101733fd447e93efc736888ba089
Source dataset
uspto-grants-2009_06
Patent number
US07550469B2

Reaction notes

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