3-Hydroxypyridine → 1,1-Dimethylethyl (2R)-2-[(3-pyridinyloxy)methyl]-1-pyrrolidinecarboxylate

HRID 1416591Notes

Reaction equation

HRID 1416591 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[C:32]([O:36][C:37]([N:39]1[CH2:43][CH2:42][CH2:41][C@@H:40]1[CH2:44][OH:45])=[O:38])([CH3:35])([CH3:34])[CH3:33].O[C:47]1[CH:48]=[N:49][CH:50]=[CH:51][CH:52]=1>O1CCCC1>[C:32]([O:36][C:37]([N:39]1[CH2:43][CH2:42][CH2:41][C@@H:40]1[CH2:44][O:45][C:47]1[CH:48]=[N:49][CH:50]=[CH:51][CH:52]=1)=[O:38])([CH3:35])([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 79713-HydroxypyridineHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 688279N-(tert-Butoxycarbonyl)-D-prolinol

Product 1

HCID 107077241,1-Dimethylethyl (2R)-2-[(3-pyridinyloxy)methyl]-1-pyrrolidinecarboxylateYield 58.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of triphenylphosphine (1.24 g, 4.74 mmol) in 20 mL of tetrahydrofuran at room temperature was added diethyl azodicarboxylate (0.746 mL, 4.74 mmol) dropwise with stirring. After stirring at room temperature for 30 minutes, (R)-1-t-butoxycarbonyl-2-pyrrolidinemethanol (350 mg, 3.16 mmol) and 3-hydroxypyridine (450 mg, 4.74 mmol) were added to the reaction mixture. The resultant solution was then stirred at room temperature overnight. After all of the starting material was consumed, the organic solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography. Elution with chloroform:methanol (10: 1) provided 518 mg of the title compound along with substantial amount of reduced DEAD reagent. MS (DCI/NH3) m/e 279 (M+H)+.

Workup

  1. stirringAfter stirring at room temperature for 30 minutes
  2. customAfter all of the starting material was consumed
  3. customthe organic solvent was evaporated in vacuo
  4. customThe residue was purified by silica gel column chromatography
  5. washElution with chloroform:methanol (10: 1)

Sources & evidence

ORD record
ord-123755523f814b8db24b7550ac350abc
Source dataset
uspto-grants-1999_06
Patent number
US05914328

Reaction notes

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