(2S)-1-Methyl-2-pyrrolidinemethanol → HCID 178480325, compound

HRID 536718Notes

Reaction equation

HRID 536718 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][OH:8].CC(C)([O-])C.[Na+].[C:15]([C:19]1[O:23]/[C:22](=[N:24]\[C:25](=[O:37])[C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=2F)/[N:21]([CH2:38][C@H:39]2[CH2:43][CH2:42][CH2:41][O:40]2)[CH:20]=1)([CH3:18])([CH3:17])[CH3:16]>C1COCC1>[C:15]([C:19]1[O:23]/[C:22](=[N:24]\[C:25](=[O:37])[C:26]2[CH:31]=[C:30]([C:32]([F:34])([F:33])[F:35])[CH:29]=[CH:28][C:27]=2[O:8][CH2:7][C@@H:3]2[CH2:4][CH2:5][CH2:6][N:2]2[CH3:1])/[N:21]([CH2:38][C@H:39]2[CH2:43][CH2:42][CH2:41][O:40]2)[CH:20]=1)([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 643492(2S)-1-Methyl-2-pyrrolidinemethanolHCID 23676156Sodium t-butoxideHCID 178441318HCID 178441318, compound

Product 1

HCID 178480325HCID 178480325, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
22 °C

Procedure

To a solution of (S)-(1-methylpyrrolidin-2-yl)methanol (Aldrich) (0.860 mL, 7.24 mmol) in 15 mL of THF was added sodium tert-butoxide (0.696 g, 7.24 mmol). The reaction was stirred at 22° C. for 20 min. The reaction was cooled to 5° C. and a solution of Example 32C (1.5 g, 3.62 mmol) in 5 mL of THF was added. The reaction was stirred at 5° C. for 2 h, then at 22° C. for 1 h. The solvent was evaporated under reduced pressure. The residue was dissolved with methylene chloride, washed with NaHCO3, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography on SiO2 using an Analogix® Intelliflash280™ (solvent A=CH2Cl2; solvent B=3 N NH3/MeOH:CH2Cl2 (1:9); eluting with A:B (100:0) changing to A:B (0:100) over the run time of approximately 30 minutes) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.17 (s, 9H), 1.53-1.98 (m, 8H), 1.97-2.15 (m, 2H), 2.19-2.35 (m, 1H), 2.46 (s, 3H), 2.62-2.81 (m, 1H), 3.07 (t, J=8.1 Hz, 1H), 3.62 (dd, J=14.1, 7.6 Hz, 1H), 3.72-3.94 (m, 2H), 4.01-4.21 (m, 2H), 6.53 (s, 1H), 6.96 (d, J=8.8 Hz, 1H), 7.55 (dd, J=9.0, 2.9 Hz, 1H), 7.93 (d, J=2.0 Hz, 1H); MS (ESI) m/z 511 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to 5° C.
  2. stirringThe reaction was stirred at 5° C. for 2 h
  3. waitat 22° C. for 1 h
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved with methylene chloride
  6. washwashed with NaHCO3
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on SiO2 using an Analogix® Intelliflash280™ (solvent A=CH2Cl2
  10. washeluting with A:B (100:0)
  11. customover the run time of approximately 30 minutes

Sources & evidence

ORD record
ord-566ec9498a1348099fb778152de3781d
Source dataset
uspto-grants-2014_10
Patent number
US08859596B2

Reaction notes

Loading…