Triphenylphosphine → HCID 59149710, compound

HRID 1675135Notes

Reaction equation

HRID 1675135 reaction equation
[CH3:1][CH:2]([O:4]C(/N=N/C(OC(C)C)=O)=O)C.[F:15][C:16]([F:40])([F:39])[C:17]1[N:21]2[N:22]=[C:23]([N:26]3[CH2:31][CH2:30][CH:29]([C:32]4[CH:33]=[C:34]([OH:38])[CH:35]=[CH:36][CH:37]=4)[CH2:28][CH2:27]3)[CH:24]=[CH:25][C:20]2=[N:19][N:18]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCCC1OCCO>C1COCC1>[F:40][C:16]([F:15])([F:39])[C:17]1[N:21]2[N:22]=[C:23]([N:26]3[CH2:31][CH2:30][CH:29]([C:32]4[CH:33]=[C:34]([CH:35]=[CH:36][CH:37]=4)[O:38][CH2:1][CH2:2][OH:4])[CH2:28][CH2:27]3)[CH:24]=[CH:25][C:20]2=[N:19][N:18]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 41668332-(Oxan-2-yloxy)ethan-1-olHCID 5363146Diisopropyl azodicarboxylateHCID 67340083HCID 67340083, compound

Product 1

HCID 59149710HCID 59149710, compoundYield 53.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIAD (0.081 mL, 0.41 mmol) was added dropwise to 3-[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenol (obtained as described in Example 670, preparation of starting materials) (125 mg, 0.34 mmol), triphenylphosphine (108 mg, 0.41 mmol) and 2-(tetrahydro-2H-pyran-2-yloxy)ethanol (60.4 mg, 0.41 mmol) in THF (3 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 4 hours, then added to an SCX column. The crude product was eluted from the column using 2M ammonia in methanol and the solvents were evaporated. The crude product was purified by flash silica chromatography, elution gradient 80 to 100% EtOAc in isohexane. Fractions containing product were evaporated then further purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(3-(1-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenoxy)ethanol (74 mg, 53%) as a solid.

Workup

  1. additionadded to an SCX column
  2. washThe crude product was eluted from the column
  3. customthe solvents were evaporated
  4. customThe crude product was purified by flash silica chromatography, elution gradient 80 to 100% EtOAc in isohexane
  5. additionFractions containing product
  6. customwere evaporated
  7. customthen further purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-35267e10a6384f4c88acb68597c98646
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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