Ammonium Chloride → HCID 69890998, compound

HRID 1837983Notes

Reaction equation

HRID 1837983 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:8]1[CH2:12][C:11](=[O:13])[N:10]([CH3:14])[C@@H:9]1[C:15](N1[C@@H](CC2C=CC=CC=2)COC1=O)=[O:16].[H-].[H-].[H-].[H-].[Li+].[Al+3].[NH4+].[Cl-]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]1[C@@H:9]([CH2:15][OH:16])[N:10]([CH3:14])[C:11](=[O:13])[CH2:12]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 21226445Aluminium lithium hydride2×HCID 59066510HCID 59066510, compound

Product 1

HCID 69890998HCID 69890998, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a −78° C. solution of (4S)-3-{[(2S,3S)-3-(2-fluorophenyl)-1-methyl-5-oxopyrrolidin-2-yl]carbonyl}-4-benzyl-1,3-oxazolidin-2-one (1.0 g, 2.5 mmol) in anhyd. THF (30 mL) was added a solution of LiAlH4 (1M in THF, 2.5 mL, 2.5 mmol, 1 equiv). After 2 h a solution of LiAlH4 (1M in THF, 0.5 mL, 0.5 mmol, 0.2 equiv) was added and after 30 min the reaction was treated with a saturated NH4Cl solution (10 mL). The resulting mixture was allowed to warm to room temperature and filtered. The filtrate was concentrated under reduced pressure and purified by flash chromatography (50 g silica gel, gradient from 0% to 10% MeOH/EtOAc) to afford (4S,5S)-4-(2-fluorophenyl)-5-(hydroxymethyl)-1-methylpyrrolidin-2-one (340 mg, 61%) as a white solid: TLC (5% MeOH/EtOAc) Rf 0.40; 1H NMR (CDCl3) δ 2.41 (dd, J=8.4, 15.8 Hz, 1H), 2.94 (s, 3H), 3.03 (dd, J=11.6, 16.0 Hz, 1H), 3.21 (dd, J=2.2, 12.5 Hz, 1H), 3.53 (br s, 1H), 3.67 (dd, J=2.2, 12.5 Hz, 1H), 3.81-3.85 (m, 1H), 3.94-4.03 (m, 1H), 7.04 (t, J=9.0 Hz, 1H), 7.15 (t, J=7.5 Hz, 1H), 7.22-7.29 (m, 1H), 7.38 (t, J=7.5 Hz, 1H); HPLC ES-MS m/z (rel abundance) 224 (MH+, 100%).

Workup

  1. customTo a −78° C.
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. custompurified by flash chromatography (50 g silica gel, gradient from 0% to 10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-425daee0f1454325bdd44506ec458f77
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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