Sodium hydride → HCID 67479956, compound

HRID 1752310Notes

Reaction equation

HRID 1752310 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.F[C:15]1[C:20]([F:21])=[CH:19][C:18]([F:22])=[CH:17][N:16]=1.[H-].[Na+]>C1COCC1.CN(C=O)C.CCOCC>[F:21][C:20]1[C:15]([O:1][C@@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)=[N:16][CH:17]=[C:18]([F:22])[CH:19]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 27832872,3,5-TrifluoropyridineHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 67479956HCID 67479956, compoundYield 47%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of (R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1.10 g, 5.89 mmol) and 2,3,5-trifluoropyridine (0.86 g, 6.48 mmol) in dry THF (20 mL) and dry DMF (4 mL), at rt was added 60% NaH in oil (0.35 g, 8.84 mmol). The mixture was stirred in a 40° C. oil bath overnight, cooled to rt, diluted with ether (175 mL), washed with water (25 mL) and brine (25 mL), and dried over Na2SO4. Removal of the solvent left a dark oil (1.94 g) which was purified by chromatography on a 40-g silica cartridge eluted with a 0-100% EtOAc in hexanes gradient to afford (R)-tert-butyl 3-(3,5-difluoropyridin-2-yloxy)pyrrolidine-1-carboxylate (0.83 g, 47%). LC-MS Method 1 tR=1.85 min, m/z=301.

Workup

  1. temperaturecooled to rt
  2. washwashed with water (25 mL) and brine (25 mL)
  3. dry with materialdried over Na2SO4
  4. customRemoval of the solvent
  5. waitleft a dark oil (1.94 g) which
  6. customwas purified by chromatography on a 40-g silica cartridge
  7. washeluted with a 0-100% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-f3674b6b22fe429c815638ef95a6f9ca
Source dataset
uspto-grants-2015_10
Patent number
US09163012B2

Reaction notes

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