Triphenylphosphine → 6-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-azidomethyl-3-methyl-butyl)-amide

HRID 632422Notes

Reaction equation

HRID 632422 reaction equation
O[CH2:2][C@@H:3]([NH:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[C:13]([O:22][CH2:23][CH:24]2[CH2:26][CH2:25]2)[N:12]=1)=[O:10])[CH2:4][CH:5]([CH3:7])[CH3:6].[N-:27]=[N+:28]=[N-:29].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C(Cl)(Cl)(Cl)Cl>[N:27]([CH2:2][C@@H:3]([NH:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:18][CH2:19][CH2:20][CH2:21]2)=[C:13]([O:22][CH2:23][CH:24]2[CH2:25][CH2:26]2)[N:12]=1)=[O:10])[CH2:4][CH:5]([CH3:6])[CH3:7])=[N+:28]=[N-:29]

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 711055406-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-hydroxymethyl-3-methyl-butyl)-amide

Product 1

HCID 711057256-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-azidomethyl-3-methyl-butyl)-amideYield 45%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a colorless solution of 6-cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-hydroxymethyl-3-methyl-butyl)-amide (Example 14b; 231 mg, 639 μmol) in DMF (25.6 mL) and CCl4 (6.4 mL) was added sodium azide (49.9 mg, 767 μmol) and triphenylphosphine (352 mg, 1.34 mmol). The resulting reaction mixture was stirred at 90° C. for 4 hours. After cooling to room temperature the solvent was removed in vacuo. The residue was partitioned between water and ethyl acetate; the organic phases were washed with brine, combined, dried with Na2SO4, filtered and concentrated in vacuo. The residue, a brown waxy solid, was purified by flash chromatography (silica gel, 50 g, 0% to 60% ethyl acetate in heptane) to give the title compound (110 mg, 45%) as white solid; MS (ESI) 387.3 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. temperatureAfter cooling to room temperature the solvent
  3. customwas removed in vacuo
  4. customThe residue was partitioned between water and ethyl acetate
  5. washthe organic phases were washed with brine
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue, a brown waxy solid, was purified by flash chromatography (silica gel, 50 g, 0% to 60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e9eb94a769fd4b33bbfa438e305117f9
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Reaction notes

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