Iodoethane → benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate

HRID 1063269Notes

Reaction equation

HRID 1063269 reaction equation
[CH2:1]([C:3]1[C:4]([NH:11][C@H:12]2[C@@H:16]([OH:17])[CH2:15][N:14]([C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[CH2:13]2)=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2].[H-].[Na+].I[CH2:31][CH3:32]>CN(C=O)C>[CH2:1]([C:3]1[C:4]([NH:11][C@H:12]2[C@@H:16]([O:17][CH2:31][CH3:32])[CH2:15][N:14]([C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[CH2:13]2)=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 60044796benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 60044802benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylateYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-hydroxypyrrolidine-1-carboxylate (17.70 g, 47.8 mmole) in DMF (0.3 M) at 0° C. under N2 was added NaH portionwise (2.48 g, 1.3 eq.). After 15 minutes, iodoethane (4.93 mL, 1.3 eq.) was added dropwise. After 2 hours, the reaction mixture was quenched with brine (200 mL), extracted with ethyl acetate (2×200 mL), dried with MgSO4, filtered and concentrated. Vacuum chromatography was run on a 1 L frit funnel (20-40% ethyl acetate in heptane gradient) to give 14.64 g (77%) of benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate as an oil. IR (liq.) 2971, 2936, 2340, 1950, 1709, 1546, 1499, 1464, 1448, 1422, 1395, 1350, 1173, 1129, 1097 (s) cm−1 HRMS (ESI) calcd for C22H30N4O3+H1 399.2396. found 399.2392. [α]25D=−50° (c 0.55, 0.1N HCl).

Workup

  1. waitAfter 2 hours
  2. customthe reaction mixture was quenched with brine (200 mL)
  3. extractionextracted with ethyl acetate (2×200 mL)
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customVacuum chromatography was run on a 1 L frit funnel

Sources & evidence

ORD record
ord-cba04da6631e46789ed544e08fe0e265
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

Loading…