Aluminium lithium hydride → HCID 131733442, compound

HRID 2277060Notes

Reaction equation

HRID 2277060 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C@H:11]([C:13]1[CH:14]=[C:15]([CH:31]=[CH:32][CH:33]=1)[O:16][CH2:17][CH:18]1[CH2:23][CH2:22][N:21]([C:24](OC(C)(C)C)=O)[CH2:20][CH2:19]1)[OH:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[OH:12][C@@H:11]([C:13]1[CH:33]=[CH:32][CH:31]=[C:15]([O:16][CH2:17][CH:18]2[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]2)[CH:14]=1)[CH2:10][CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 90404382HCID 90404382, compound

Product 1

HCID 131733442HCID 131733442, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-tert-Butyl 4-((3-(3-((tert-butoxycarbonyl)amino)-1-hydroxypropyl)phenoxy)methyl)piperidine-1-carboxylate (0.70 g, 1.50 mmol) was added at 0° C. to a suspension of LiAlH4 (0.171 g, 4.5 mmol) in anhydrous THF (10 mL) and the reaction mixture was stirred at room temperature for 1 h. After completion of the reaction as judged by TLC, the reaction mixture was quenched with EtOAc (10 mL) and 10% aqueous NaOH, filtered through Celite, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by column chromatography (CH2Cl2-10% MeOH:CH2Cl2, 0-5% gradient) gave (R)-tert-butyl (3-hydroxy-3-(3-((1-methylpiperidin-4-yl)methoxy)phenyl)propyl)carbamate as a pale yellow semi-solid. Yield (0.50 g, 87%); 1H NMR (400 MHz, CDCl3): δ 7.22 (t, J=4.40 Hz, 1H), 6.92 (s, 2H), 6.76 (d, J=8.0 Hz, 1H), 4.31 (s, 1H), 3.85 (d, J=5.6 Hz, 2H), 3.69 (s, 1H), 3.27 (d, J=6.8 Hz, 2H), 2.58 (s, 2H), 2.46 (s, 2H), 2.04-1.91 (m, 4H), 1.84 (t, J=5.20 Hz, 4H), 1.70-1.67 (m, 1H), 1.45 (s, 9H); MS: m/z 379.28 [M+H]+.

Workup

  1. customAfter completion of the reaction
  2. customthe reaction mixture was quenched with EtOAc (10 mL) and 10% aqueous NaOH
  3. filtrationfiltered through Celite
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography (CH2Cl2-10% MeOH:CH2Cl2, 0-5% gradient)

Sources & evidence

ORD record
ord-9a9ddb554adb410084a5590328378567
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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