(2S)-1-Methyl-2-pyrrolidinemethanol → HCID 178448484, compound

HRID 340641

Reaction equation

HRID 340641 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.[K+].[CH2:15]([N:19]1[CH:23]=[C:22]([C:24]([CH3:27])([CH3:26])[CH3:25])[S:21]/[C:20]/1=[N:28]\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=1F)[CH2:16][CH2:17][CH3:18]>C1COCC1>[CH2:15]([N:19]1[CH:23]=[C:22]([C:24]([CH3:26])([CH3:27])[CH3:25])[S:21]/[C:20]/1=[N:28]\[C:29](=[O:41])[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:37])[F:38])[CH:33]=[CH:32][C:31]=1[O:8][CH2:7][C@@H:3]1[CH2:4][CH2:5][CH2:6][N:2]1[CH3:1])[CH2:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 643492(2S)-1-Methyl-2-pyrrolidinemethanolHCID 23665647Potassium tert-butoxideHCID 178448483HCID 178448483, compound

Product 1

HCID 178448484HCID 178448484, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-(1-methylpyrrolidin-2-yl)methanol (109 mg, 0.94 mmol) in THF (5 mL) was treated with 1 M solution of potassium t-butoxide (0.95 mL, 0.944 mmol) and stirred for 15 min. A solution of Example 9B (190 mg, 0.47 mmol) was added to the reaction mixture and stirred for 6 hours. The reaction mixture was quenched with saturated NH4Cl solution, concentrated in vacuo, partitioned between EtOAc and brine, dried (MgSO4), filtered, and concentrated. The residue was purified using an Analogix® Intelliflash280™ (SiO2, 0-15% methanol in dichloromethane) to afford the title compound (175 mg, 75% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (t, J=7.3 Hz, 3H), 1.17-1.42 (m, 11H), 1.49-1.83 (m, 5H), 1.82-2.03 (m, 1H), 2.17 (q, J=8.7 Hz, 1H), 2.32 (s, 3H), 2.54-2.67 (m, 1H), 2.83-3.01 (m, 1H), 3.92-4.10 (m, 2H), 4.14 (t, J=7.3 Hz, 2H), 7.28 (d, J=8.8 Hz, 1H), 7.32 (s, 1H), 7.72 (dd, J=9.0, 2.2 Hz, 1H), 7.95 (d, J=2.0 Hz, 1H). MS (DCI/NH3) m/z 498 (M+H)+. Anal. calcd for C25H34F3N3O2S: C, 60.34; H, 6.99; N, 8.44. Found: C, 60.27; H, 7.09; N, 8.40.

Workup

  1. stirringstirred for 6 hours
  2. customThe reaction mixture was quenched with saturated NH4Cl solution
  3. concentrationconcentrated in vacuo
  4. custompartitioned between EtOAc and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified

Sources & evidence

ORD record
ord-4ccecf0356e74823b988194a80eb604e
Source dataset
uspto-grants-2014_11
Patent number
US08895592B2

Linked notes

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