(5S)-5-(Hydroxymethyl)-1-methyl-2-pyrrolidinone → HCID 178481529, compound

HRID 82767Notes

Reaction equation

HRID 82767 reaction equation
[OH:1][CH2:2][C@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][CH2:4]1.CC(C)([O-])C.[Na+].[C:16]([C:20]1[S:24]/[C:23](=[N:25]\[C:26](=[O:38])[C:27]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=2F)/[N:22]([CH2:39][C@H:40]2[CH2:44][CH2:43][CH2:42][O:41]2)[CH:21]=1)([CH3:19])([CH3:18])[CH3:17]>C1COCC1>[C:16]([C:20]1[S:24]/[C:23](=[N:25]\[C:26](=[O:38])[C:27]2[CH:32]=[C:31]([C:33]([F:35])([F:34])[F:36])[CH:30]=[CH:29][C:28]=2[O:1][CH2:2][C@@H:3]2[CH2:4][CH2:5][C:6](=[O:9])[N:7]2[CH3:8])/[N:22]([CH2:39][C@H:40]2[CH2:44][CH2:43][CH2:42][O:41]2)[CH:21]=1)([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 14876039(5S)-5-(Hydroxymethyl)-1-methyl-2-pyrrolidinoneHCID 23676156Sodium t-butoxideHCID 178441320HCID 178441320, compound

Product 1

HCID 178481529HCID 178481529, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
22 °C

Procedure

To a solution of (S)-5-(hydroxymethyl)-1-methylpyrrolidin-2-one (108 mg, 0.84 mmol) (Williams, P. D. et al. Journal of Medicinal Chemistry 1991, 34, 887-900) in 5 mL of THF was added sodium tert-butoxide (100 mg, 1.05 mmol). The mixture was stirred at 22° C. for 20 minutes. The mixture was cooled to 5° C. and a solution of Example 1A (180 mg, 0.42 mmol) in 2 mL of THF was added. The mixture was stirred at 5° C. for 2 hours, then at 22° C. for 1 hour. The solvent was evaporated under reduced pressure. The residue was dissolved in methylene chloride, washed with water, dried over MgSO4 and concentrated. The residue was purified by flash chromatography on SiO2 using an Analogix® Intelliflash280™ (eluted with CH2Cl2:10% MeOH and 3N NH3 in CH2Cl2: 0 to 100%) to afford the title compound; 1H NMR (300 MHz, CDCl3) δ ppm 1.36 (s, 9 H), 1.58-1.73 (m, 1 H), 1.74-2.14 (m, 4 H), 2.14-2.42 (m, 2 H), 2.44-2.64 (m, 1 H), 2.91 (s, 3 H), 3.72-3.91 (m, 2 H), 3.93-4.03 (m, 1H), 4.07 (dd, J=12.0, 4.8 Hz, 1 H), 4.14-4.32 (m, 3 H), 4.39 (dd, J=13.3, 2.6 Hz, 1 H), 6.88 (s, 1 H), 6.99 (d, J=8.7 Hz, 1 H), 7.60 (dd, J=8.7, 2.4 Hz, 1 H), 8.11 (d, J=2.4 Hz, 1 H); MS (ESI) m/z 540 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to 5° C.
  2. stirringThe mixture was stirred at 5° C. for 2 hours
  3. waitat 22° C. for 1 hour
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in methylene chloride
  6. washwashed with water
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on SiO2 using
  10. washan Analogix® Intelliflash280™ (eluted with CH2Cl2:10% MeOH and 3N NH3 in CH2Cl2: 0 to 100%)

Sources & evidence

ORD record
ord-28e7ce224bf049129438164bfc38a0cc
Source dataset
uspto-grants-2014_09
Patent number
US08846730B2

Reaction notes

Loading…