Aluminium lithium hydride → HCID 54670219, compound

HRID 1186228Notes

Reaction equation

HRID 1186228 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([N:14]1[CH2:29][CH2:28][N:17]2[C:18]3[N:27]=[CH:26][CH:25]=[CH:24][C:19]=3[NH:20][C:21](=O)[CH2:22][CH:16]2[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>O1CCCC1>[CH2:7]([N:14]1[CH2:29][CH2:28][N:17]2[C:18]3[N:27]=[CH:26][CH:25]=[CH:24][C:19]=3[NH:20][CH2:21][CH2:22][CH:16]2[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 67001978HCID 67001978, compound

Product 1

HCID 54670219HCID 54670219, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Solid LiAlH4 (255 mg, 6.72 mmol) was added gradually to a stirred suspension of the product of Example 51B (337 mg, 1.093 mmol) in tetrahydrofuran (25 mL). The resulting mixture was heated at reflux under nitrogen for 1 hour, then cooled in ice and quenched by successive addition of ethyl acetate (3 mL), water (0.25 mL), 15% NaOH (0.25 mL) and water (0.75 mL). The gray slurry was filtered through diatomaceous earth with an ethyl acetate (30 mL total) rinse. The filtrate was concentrated under vacuum and the residue was purified by HPLC (30×100 mm, C18, XBridge™ column eluting with aqueous 0.1 M (NH4)2CO3— methanol, 80:20-0:100 over 15 minutes) to provide the title compound: 1H NMR (300 MHz, CD3OD) δ ppm 1.75-1.89 (m, 1H), 1.90-2.04 (m, 1H), 2.30 (dd, J=11.0, 9.0 Hz, 1H), 2.44 (ddd, J=10.9, 9.6, 3.2 Hz, 1H), 2.59 (ddd, J=10.9, 2.8, 1.2 Hz, 1H), 2.72-2.83 (m, 1H), 3.17 (ddd, J=12.5, 5.4, 3.7 Hz, 1H), 3.26-3.34 (m, 1H), 3.33-3.53 (m, 3H), 3.52-3.63 (m, 2H), 6.73 (dd, J=7.8, 4.7 Hz, 1H), 6.91 (dd, J=7.6, 1.5 Hz, 1H), 7.20-7.40 (m, 5H), 7.61 (dd, J=4.9, 1.5 Hz, 1H); MS (ESI) m/z 295 (M+H)+.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux under nitrogen for 1 hour
  3. temperaturecooled in ice
  4. customquenched by successive addition of ethyl acetate (3 mL), water (0.25 mL), 15% NaOH (0.25 mL) and water (0.75 mL)
  5. filtrationThe gray slurry was filtered through diatomaceous earth with an ethyl acetate (30 mL total)
  6. washrinse
  7. concentrationThe filtrate was concentrated under vacuum
  8. customthe residue was purified by HPLC (30×100 mm, C18, XBridge™ column eluting with aqueous 0.1 M (NH4)2CO3— methanol, 80:20-0:100 over 15 minutes)

Sources & evidence

ORD record
ord-469ba85f19584b5cb396218cebcb8cf2
Source dataset
uspto-grants-2014_03
Patent number
US08673896B2

Reaction notes

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