Diethylamine → HCID 86670434, compound

HRID 1972681Notes

Reaction equation

HRID 1972681 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:22]([OH:31])([C:27]([F:30])([F:29])[F:28])[C:23]([F:26])([F:25])[F:24])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)(=[O:16])=[O:15])[CH2:10][CH2:9]1.C[Si](C)(C)[C:34]#[C:35][CH3:36].C(NCC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu](I)I.CN(C=O)C>[F:24][C:23]([F:26])([F:25])[C:22]([C:4]1[CH:5]=[CH:6][C:7]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([C:17]3[S:18][CH:19]=[CH:20][CH:21]=3)(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[C:2]([C:34]#[C:35][CH3:36])[CH:3]=1)([OH:31])[C:27]([F:30])([F:29])[F:28]

Participants

8

Reactant 4

HCID 8021DiethylamineHCID 11776TriphenylphosphineHCID 803631-(Trimethylsilyl)prop-1-yneHCID 86670331HCID 86670331, compound

Product 1

HCID 86670434HCID 86670434, compoundYield 23.8%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with 2-(3-bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (128 mg, 0.23 mmol, Example 69, step 2), 1-(trimethylsilyl)-1-propyne (0.173 mL, 1.16 mmol, Sigma-Aldrich, St. Louis, Mo.), diethylamine (48 μL, 0.46 mmol, Sigma-Aldrich, St. Louis, Mo.), bis(triphenylphosphine) palladium(II) dichloride (15 mg, 0.02 mmol, Strem Chemical Inc, Newburyport, Mass.), triphenylphosphine (12 mg, 0.05 mmol, Sigma-Aldrich, St. Louis, Mo.), copper iodide (9 mg, 0.05 mmol, Strem Chemical Inc, Newburyport, Mass.), and DMF (1 mL). The reaction mixture was purged with nitrogen for several minutes, and then stirred and heated in an Emrys Optmizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 30 min. The reaction was diluted with EtOAc (about 10 mL) and water (about 10 mL). The organic layer was separated and washed with water (10 mL), dried (Na2SO4), concentrated and purified column chromatography (12 g silica, 0 to 20% EtOAc in hexanes to afford 1,1,1,3,3,3-hexafluoro-2-(3-(1-propyn-1-yl)-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (28 mg) as a white solid.

Workup

  1. customA glass microwave reaction vessel
  2. customThe reaction mixture was purged with nitrogen for several minutes
  3. additionThe reaction was diluted with EtOAc (about 10 mL) and water (about 10 mL)
  4. customThe organic layer was separated
  5. washwashed with water (10 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified column chromatography (12 g silica, 0 to 20% EtOAc in hexanes

Sources & evidence

ORD record
ord-082a8b13a00b47f685dbd1cc2de7fc58
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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