Diisopropylethylamine → HCID 118659413, compound

HRID 1477238Notes

Reaction equation

HRID 1477238 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]([O:17][CH3:18])=[O:16])[CH:10]=2)=[CH:5][CH:4]=1)#[CH:2].CCN([CH:25]([CH3:27])[CH3:26])C(C)C>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[OH:16][CH2:15][C@@H:11]1[CH2:10][C@H:27]1[C:25]#[C:26][C:2]#[C:1][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]([O:17][CH3:18])=[O:16])[CH:10]=2)=[CH:7][CH:8]=1

Participants

6

Reactant 2

HCID 81531DiisopropylethylamineHCID 118659408HCID 118659408, compound

Product 1

HCID 118659413HCID 118659413, compoundYield 45.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of compound 2.6 (1.77 g, 7.5 mmol), Pd(PPh3)2Cl2 (262 mg, 0.37 mmol), CuI (143 mg, 0.75 mmol), and DIPEA (2.9 g, 22.5 mmol) in THF (50 mL) was added compound 2.8 (1.84 g, 10.5 mmol) under an argon atmosphere, and the mixture was stirred at room temperature for 5 hr. The solvent was removed under reduced pressure, and the resulting residue was diluted with water (100 mL) and extracted with EtOAc (3×150 mL). The combined organic layers were dried and concentrated under reduced pressure to give a red oil, which was purified by flash chromatography (silica gel/PE:EA 5:1˜3:1) to yield methyl 4-(4-(((trans)-2-(hydroxymethyl)cyclopropyl)buta-1,3-diyn-1-yl)phenyl)picolinate (2.9, 570 mg, 23%): MS: m/z calcd for C21H17NO3 331.12. found [M+H]+ 332; 1H-NMR (DMSO-d6, 400 MHz) δ 8.77 (d, J=5.6 Hz, 1H), 8.30 (s, 1H), 7.99 (d, J=5.6 Hz, 1H), 7.90 (d, J=8.4 Hz, 2H), 7.67 (d, J=8.4 Hz, 2H), 4.72 (t, J=5.6 Hz, 1H), 3.91 (s, 3H), 3.44 (m, 1H), 3.24 (m, 1H), 1.45 (m, 2H), 0.88 (m, 2H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe resulting residue was diluted with water (100 mL)
  3. extractionextracted with EtOAc (3×150 mL)
  4. customThe combined organic layers were dried
  5. concentrationconcentrated under reduced pressure
  6. customto give a red oil, which
  7. customwas purified by flash chromatography (silica gel/PE:EA 5:1˜3:1)

Sources & evidence

ORD record
ord-9e5721f776334885af06d78b4b42ba19
Source dataset
uspto-grants-2016_08
Patent number
US09403758B2

Reaction notes

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