Aluminium lithium hydride → 4-[((S)-4,4-difluoro-pyrrolidin-2-ylmethyl)-amino]-adamantan-1-ol

HRID 1644806Notes

Reaction equation

HRID 1644806 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH:11]3[NH:18][C:19]([C@@H:21]3[CH2:25][C:24]([F:27])([F:26])[CH2:23][NH:22]3)=O)[CH2:9]1)[CH2:15]2>C1COCC1>[F:27][C:24]1([F:26])[CH2:23][NH:22][C@H:21]([CH2:19][NH:18][CH:11]2[CH:12]3[CH2:17][C:8]4([OH:7])[CH2:15][CH:14]([CH2:16][CH:10]2[CH2:9]4)[CH2:13]3)[CH2:25]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 66773511(S)-4,4-difluoro-pyrrolidine-2-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide

Product 1

HCID 667745474-[((S)-4,4-difluoro-pyrrolidin-2-ylmethyl)-amino]-adamantan-1-olYield 43.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminium hydride (0.51 g) was added in portions to the solution of (S)-4,4-difluoro-pyrrolidine-2-carboxylic acid (5-hydroxy-adamantan-2-yl)-amide (1.2 g) in THF (15 mL) at RT. The reaction mixture was refluxed for 24 h. The reaction mixture was quenched with saturated aqueous sodium sulfate solution (15 mL) at 0° C., filtered through Celite® and extracted with ethyl acetate (3×10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under high vacuum using rotary evaporator to give a crude material, which was purified through column chromatography (3% MeOH:DCM, silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 7 inch) to afford the desired 4-[((S)-4,4-difluoro-pyrrolidin-2-ylmethyl)-amino]-adamantan-1-ol as a white solid (0.5 g).

Workup

  1. temperatureThe reaction mixture was refluxed for 24 h
  2. customThe reaction mixture was quenched with saturated aqueous sodium sulfate solution (15 mL) at 0° C.
  3. filtrationfiltered through Celite®
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated under high vacuum
  7. customevaporator
  8. customto give a crude material, which
  9. customwas purified through column chromatography (3% MeOH:DCM, silica 100-200 mesh, Diameter of column—2.5 cm, Height of silica—approx. 7 inch)

Sources & evidence

ORD record
ord-7c85ee80537b4f82a7570370869ce7c9
Source dataset
uspto-grants-2012_02
Patent number
US08124636B2

Reaction notes

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