Trimethylamine → HCID 68865337, compound

HRID 1726023Notes

Reaction equation

HRID 1726023 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:17]([O:23][CH3:24])[C:16]([CH2:25][CH3:26])=[CH:15][CH:14]=1)(=[O:11])=[O:10].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:46][CH2:47][CH2:48][C:49]#[CH:50].CN(C)C>C1COCC1.[Pd](Cl)Cl.[Cu]I>[CH2:25]([C:16]1[C:17]([O:23][CH3:24])=[C:18]([C:13]([NH:12][S:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[C:50]#[C:49][CH2:48][CH2:47][OH:46])(=[O:11])=[O:10])=[CH:14][CH:15]=1)[C:19]([O:21][CH3:22])=[O:20])[CH3:26]

Participants

8

Reactant 4

HCID 1146TrimethylamineHCID 11776TriphenylphosphineHCID 135663-Butyn-1-OLHCID 68863098HCID 68863098, compound

Product 1

HCID 68865337HCID 68865337, compound

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A solution of Example 615A (0.446 g, 1.0 mmol), bis(triphenylphosphine))palladium dichloride (35 mg, 0.05 mmol), triphenylphosphine (6.5 mg, 0.025 mmol), 4-hydroxy-1-butyne (0.14 g, 2.0 mmol) and trimethylamine (0.2 mL, 1.5 mmol) in anhydrous THF (6 mL) in a scintillation vial was shaken at ambient temperature for 20 minutes. Copper (I) iodide (5 mg, 0.025 mmol) was added. The mixture was purged with argon, sealed and shaken at 75° C. for 8 hours, treated with ethyl acetate (30 mL), washed with brine (2×10 mL), dried (MgSO4), filtered, and concentrated. The residue was purified on a silica gel column eluting with 30% ethyl acetate in hexanes to provide the desired product, 304 mg, 69.9%. 1H NMR (DMSO-d6) δ 1.11 (t, 3H), 2.55 (q, 2H), 2.61 (t, 2H), 3.63 (t, 2H), 3.73 (s, 3H), 5.25 (t, 1H), 6.86 (d, 1H), 7.25 (d, 1H), 7.32 (t, 1H), 7.52 (d, 2H), 7.82 (dd, 1H), 9.59 (s, 1H); MS (ESI(−)) m/e 434 (M−H)−.

Workup

  1. customThe mixture was purged with argon
  2. customsealed
  3. additiontreated with ethyl acetate (30 mL)
  4. washwashed with brine (2×10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on a silica gel column
  9. washeluting with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5a23e8e40592445f85cbe16d51707748
Source dataset
uspto-grants-2009_02
Patent number
US07491718B2

Reaction notes

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