Aluminium lithium hydride → HCID 54670026, compound

HRID 2279222Notes

Reaction equation

HRID 2279222 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([N:14]1[CH2:29][CH2:28][N:17]2[C:18]3[CH: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[CH: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 58284927HCID 58284927, compound

Product 1

HCID 54670026HCID 54670026, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Solid LiAlH4 (180 mg, 4.74 mmol) was added at room temperature to a stirring solution of the product of Example 26C (280 mg, 0.911 mmol) in tetrahydrofuran (10 mL). The resulting mixture was stirred at room temperature under nitrogen for 12 hours, then heated at 60° C. for 1 hour. The reaction mixture was cooled in ice and quenched by successive addition of ethyl acetate (4 mL), water (0.18 mL), 15% NaOH (0.18 mL) and water (0.54 mL). The mixture was filtered through diatomaceous earth with an ethyl acetate (25 mL) rinse. The filtrate was concentrated and the residue was purified by preparative HPLC (30×100 mm, C18, Waters XBridge™ column eluted with 0.1 M (NH4)2CO3(aq)-methanol (95:5-10:90) over 18 minutes) to provide the title compound: 1H NMR (400 MHz, CD3OD) δ ppm 1.53-1.63 (m, 1H), 1.94-2.06 (tddd, J=12.0, 12.0, 6.1, 3.2, 3.1 Hz, 1H), 2.29 (t, J=10.4 Hz, 1H), 2.37 (td, J=10.8, 3.1 Hz, 1H), 2.63 (ddd, J=10.5, 2.6, 2.2 Hz, 1H), 2.85 (dq, J=11.0, 2.7 Hz, 1H), 2.90-3.01 (m, 2H), 3.09 (ddd, J=12.2, 5.2, 2.7 Hz, 1H), 3.21 (td, J=11.1, 2.9 Hz, 1H), 3.53 (td, J=12.1, 1.5 Hz, 1H), 3.58 (s, 2H), 6.62 (dd, J=7.6, 1.5 Hz, 1H), 6.73 (td, J=7.6, 1.7 Hz, 1H), 6.80 (td, J=7.6, 1.7 Hz, 1H), 6.89 (dd, J=7.9, 1.5 Hz, 1H), 7.23-7.29 (m, 1H), 7.29-7.39 (m, 4H); MS (ESI) m/z 294 (M+H)+.

Workup

  1. temperatureheated at 60° C. for 1 hour
  2. temperatureThe reaction mixture was cooled in ice
  3. customquenched by successive addition of ethyl acetate (4 mL), water (0.18 mL), 15% NaOH (0.18 mL) and water (0.54 mL)
  4. filtrationThe mixture was filtered through diatomaceous earth with an ethyl acetate (25 mL)
  5. washrinse
  6. concentrationThe filtrate was concentrated
  7. customthe residue was purified by preparative HPLC (30×100 mm, C18, Waters XBridge™ column eluted with 0.1 M (NH4)2CO3(aq)-methanol (95:5-10:90) over 18 minutes)

Sources & evidence

ORD record
ord-bd201b9708814019be2def393d68dd98
Source dataset
uspto-grants-2015_09
Patent number
US09133206B2

Reaction notes

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