Aluminium lithium hydride → HCID 11770884, compound

HRID 924747Notes

Reaction equation

HRID 924747 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(O[C:15](=O)[NH:16][CH2:17][CH:18]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:26]=[N:27][NH:28][CH:29]=2)=[CH:21][CH:20]=1)C1C=CC=CC=1>O1CCCC1>[F:36][C:33]1[CH:32]=[CH:31][C:30]([CH:18]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:29]=[N:28][NH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:17][NH:16][CH3:15])=[CH:35][CH:34]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 59331976HCID 59331976, compound

Product 1

HCID 11770884HCID 11770884, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminium hydride (5.3 ml, 5.30 mmol, 1M in tetrahydrofuran) was slowly added to {2-(4-Fluoro-phenyl)-2-[4-(1H-pyrazol-4-yl)-phenyl]-ethyl}-carbamic acid benzyl ester (439 mg, 1.06 mmol) in tetrahydrofuran (5 ml) at 0° C. under nitrogen. The reaction mixture was allowed to warm to room temperature, stirred for 51 hours and quenched with water (5 ml), aqueous sodium hydroxide (2N, 5 ml) and ethyl acetate (10 ml). The aqueous layer was separated, extracted with ethyl acetate (2×20 ml). The combined organic liquors were washed with saturated aqueous brine then dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (SiO2), eluting with dichloromethane:methanol:acetic acid:water (120:15:3:2) gradient to (90:18:3:2) to afford the title compound, which was subsequently converted to the hydrochloride salt (100 mg, 32%). LC/MS: (PS-A2) Rt 1.87 [M+H]+ 296. 1H NMR (Me-d3-OD) δ 8.20 (2H, s), 7.57 (2H, d), 7.34-7.29 (4H, m), 7.02 (2H, t), t), 4.32 (1H, t), 3.67 (2H, d), 2.65 (3H, s).

Workup

  1. customquenched with water (5 ml), aqueous sodium hydroxide (2N, 5 ml) and ethyl acetate (10 ml)
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (2×20 ml)
  4. washThe combined organic liquors were washed with saturated aqueous brine
  5. dry with materialthen dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2)
  8. washeluting with dichloromethane:methanol:acetic acid:water (120:15:3:2) gradient to (90:18:3:2)

Sources & evidence

ORD record
ord-4d444b52c43c4163aaff64e41fa4c859
Source dataset
uspto-grants-2016_03
Patent number
US09283226B2

Reaction notes

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