Hexachloroethane → (S)-3-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-morpholine-4-carboxylic acid tert-butyl ester

HRID 1402259Notes

Reaction equation

HRID 1402259 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]1[C:14]([NH:16][NH:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=1)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]1[C:14]1[N:19]2[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]2=[N:17][N:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86687108(R)-3-[N'-(5-Fluoro-pyridin-2-yl)-hydrazinocarbonyl]-morpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 89624180(S)-3-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-morpholine-4-carboxylic acid tert-butyl esterYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate 83a (375 mg, 1.10 mmol), Ph3P (578 mg, 2.20 mmol) and Et3N (614 μL, 4.41 mmol) in THF (11.0 mL) at 0° C. was added hexachloroethane (523 mg, 2.20 mmol). The reaction was stirred at RT overnight then partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was taken up in MeOH and loaded onto an SCX-2 cartridge, which was washed with MeOH and eluted with 2M NH3 in MeOH; concentration in vacuo gave the title compound (297 mg, 84%). LCMS (Method 1): Rt 2.73, m/z 323.2 [MH+].

Workup

  1. customthen partitioned between EtOAc and water
  2. extractionThe aqueous layer was then extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. washwas washed with MeOH
  8. washeluted with 2M NH3 in MeOH
  9. concentrationconcentration in vacuo

Sources & evidence

ORD record
ord-04eaeb86100f431dbd56c4738ef066b7
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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