Aluminium lithium hydride → HCID 54670219, compound

HRID 2279226Notes

Reaction equation

HRID 2279226 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-106bec6ac48646cf95e21c94f54608bd
Source dataset
uspto-grants-2015_09
Patent number
US09133206B2

Reaction notes

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