Triethylamine → HCID 90404512, compound

HRID 2277078Notes

Reaction equation

HRID 2277078 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[O:5][CH2:6][CH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[CH2:16]([NH:19][C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])[CH:17]=[CH2:18].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(CC)CC>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C>[F:22][C:21]([F:24])([F:23])[C:20]([NH:19][CH2:16]/[CH:17]=[CH:18]/[C:2]1[CH:15]=[CH:14][CH:13]=[C:4]([O:5][CH2:6][CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)[CH:3]=1)=[O:25]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 558569N-Allyl-2,2,2-trifluoroacetamideHCID 532112724-[(3-Bromophenoxy)methyl]oxane

Product 1

HCID 90404512HCID 90404512, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-((3-bromophenoxy)methyl)tetrahydro-2H-pyran (1.86 g, 6.86 mmol), N-allyl-2,2,2-trifluoroacetamide (1.14 g, 7.45 mmol), P(o-Tol)3 (0.31 g, 1.02 mmol), Pd(OAc)2 (0.12 g, 0.534 mmol), Et3N (2.0 mL, 14.35 mmol) and anhydrous DMF (10 mL) was degassed by bubbling Ar for at least 5 mins, then applying vacuum/Ar once. The reaction mixture was heated under Ar at +90° C. for 20 hrs then concentrated under reduced pressure. Aqueous NH4Cl was added to the residue and extracted twice with EtOAc. Combined organic layers were washed with brine, treated with activated charcoal and dried over anhydrous MgSO4 and concentrated under reduced pressure. Purification by flash chromatography (20%-50% EtOAc-hexanes gradient) gave (E)-2,2,2-trifluoro-N-(3-(3-((tetrahydro-2H-pyran-4-yl)methoxy)phenyl)allyl)acetamide as a light yellow oil. Yield (2.01 g, 85%); 1H NMR (400 MHz, DMSO-d6) δ 9.70 (m, 1H), 7.21 (t, J=7.63 Hz, 1H), 6.94-7.00 (m, 2H), 6.78-6.83 (m, 1H), 6.48 (d, J=15.85 Hz, 1H), 6.25 (dt, J=15.85, 5.87 Hz, 1H), 3.90-4.00 (m, 2H), 3.75-3.90 (m, 4H), 3.31 (t, J=11.74 Hz, 2H), 1.90-2.04 (m, 1H), 1.60-1.70 (m, 2H), 1.24-1.37 (m, 2H).

Workup

  1. customwas degassed
  2. customby bubbling Ar for at least 5 mins
  3. temperatureThe reaction mixture was heated under Ar at +90° C. for 20 hrs
  4. concentrationthen concentrated under reduced pressure
  5. additionAqueous NH4Cl was added to the residue
  6. extractionextracted twice with EtOAc
  7. washCombined organic layers were washed with brine
  8. additiontreated with activated charcoal
  9. dry with materialdried over anhydrous MgSO4
  10. concentrationconcentrated under reduced pressure
  11. customPurification by flash chromatography (20%-50% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-0624a3291ee4476baf34b8b0ca270224
Source dataset
uspto-grants-2015_09
Patent number
US09133154B2

Reaction notes

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