(Diethylamino)sulfur trifluoride → HCID 58203893, compound

HRID 708277Notes

Reaction equation

HRID 708277 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](O)([C:14]2[CH:35]=[CH:34][C:17]3[C:18]4[N:19]=[C:20]([C:26]5[N:27]([CH:31]([CH3:33])[CH3:32])[N:28]=[CH:29][N:30]=5)[S:21][C:22]=4[CH2:23][CH2:24][O:25][C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(S(F)(F)[F:43])CC>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([F:43])([C:14]2[CH:35]=[CH:34][C:17]3[C:18]4[N:19]=[C:20]([C:26]5[N:27]([CH:31]([CH3:33])[CH3:32])[N:28]=[CH:29][N:30]=5)[S:21][C:22]=4[CH2:23][CH2:24][O:25][C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 582038674-hydroxy-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 58203893HCID 58203893, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-hydroxy-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester, from Example 511, (80 mg, 0.16 mmol) in DCM (8 mL) at −78° C. was added DAST (200 μL, 1.52 mmol). The reaction mixture was stirred at −78° C. for 30 min then allowed to warm to RT and stirred for 16 h. The reaction mixture was stirred at RT for 16 h then diluted with DCM (20 mL) and washed with saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with DCM (3×5 mL) and the combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, 20% ethyl acetate in DCM) to give 4-Fluoro-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester (45 mg, 56%). LCMS: RT=5.05 min, [M+H]+=514

Workup

  1. temperatureto warm to RT
  2. stirringstirred for 16 h
  3. stirringThe reaction mixture was stirred at RT for 16 h
  4. washwashed with saturated aqueous sodium bicarbonate solution
  5. extractionThe aqueous layer was extracted with DCM (3×5 mL)
  6. dry with materialthe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ab534ceda908410ea0e28cbf415eeee3
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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