Pyrrolidine → (R)-tert-butyl 2-(pyrrolidine-1-carbonyl)morpholine-4-carboxylate

HRID 931316Notes

Reaction equation

HRID 931316 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2[N:13]=[CH:14][CH:15]=[CH:16][C:11]=2N=N1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][O:35][C@@H:34]([C:38]([OH:40])=O)[CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(N(C(C)C)CC)(C)C.N1CCCC1>ClCCl>[N:13]1([C:38]([C@@H:34]2[O:35][CH2:36][CH2:37][N:32]([C:30]([O:29][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:31])[CH2:33]2)=[O:40])[CH2:14][CH2:15][CH2:16][CH2:11]1

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 6559076(2R)-4-((tert-butoxy)carbonyl)morpholine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 117966471(R)-tert-butyl 2-(pyrrolidine-1-carbonyl)morpholine-4-carboxylateYield 50.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′,-tetramethyluronium hexafluorophosphate (HATU) (1.47 g, 4.3 mmol) was added to a solution of (R)-4-(tert-butoxycarbonyl)morpholine-2-carboxylic acid (1 g, 4.3 mmol) and diisopropylethylamine (1.11 g, 8.6 mmol) in anhydrous dichloromethane (20 mL) at room temperature. Pyrrolidine (0.45 mL, 5.62 mmol) was added and the reaction mixture was stirred at room temperature for 2 h. The mixture was partitioned between water and dichloromethane. The organics were dried over sodium sulfate and concentrated under reduced pressure and the resulting residue was purified via column chromatography (100-200 mesh silica gel, 0-0.5% methanol in dichloromethane) to afford (R)-tert-butyl 2-(pyrrolidine-1-carbonyl)morpholine-4-carboxylate (0.62 g).

Workup

  1. customThe mixture was partitioned between water and dichloromethane
  2. dry with materialThe organics were dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customthe resulting residue was purified via column chromatography (100-200 mesh silica gel, 0-0.5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-45286df1fb8b40ff86464aaf57037ec6
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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