Diisopropylamine → HCID 22499798, compound

HRID 1815118Notes

Reaction equation

HRID 1815118 reaction equation
[CH:1]1([C:6]([OH:19])([C:17]#[CH:18])[CH2:7][C:8]2[O:13][C:12]([CH3:15])([CH3:14])[O:11][C:10](=[O:16])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:21]1[S:22][CH:23]=[CH:24][N:25]=1.C(NC(C)C)(C)C>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.CN(C=O)C>[CH:1]1([C:6]([OH:19])([C:17]#[C:18][C:21]2[S:22][CH:23]=[CH:24][N:25]=2)[CH2:7][C:8]2[O:13][C:12]([CH3:15])([CH3:14])[O:11][C:10](=[O:16])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 7912DiisopropylamineHCID 764302-BromothiazoleHCID 224998026-(2-Cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-one

Product 1

HCID 22499798HCID 22499798, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of 6-(2-cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-one (264.1 mg, 1.0; prepared as described in Example 1, Step 2), 2-bromothiazole (99.1 μL, 1.1 mmol), diisopropylamine (1.5 mL), and DMF (0.5 mL), under argon, was added Pd(PPh3)2Cl2 (28.1 mg, 0.04 mmol) and Cul (15.2 mg, 0.08 mmol). The resulting mixture was vacuum-flushed with argon (3×), then placed in 100° C. oil bath for 5 minutes, during which time the reaction becomes black/brown in color. The mixture was filtered through a plug of silica eluted with ethylacetate, concentrated, and purified by flash chromatography using 30% EtOAc/Hex as the eluent. The yield of product was 280 mg (81% yield). 1H NMR (CDCl3): δ 1.63 (m, 4H), 1.72 (s, 3H), 1.73 (s, 3H), 2.23 (pentet, 1H, J=8.0 Hz), 2.54 (s, 1H), 2.65 (s, 2H), 3.81 (s, 3H), 5.47 (s, 1H), 6.83 (d, 2H, J=8.7 Hz), 7.31(d, 2H, J=8.1 Hz), ESIMS (M+Na+): 393.2.

Workup

  1. customThe resulting mixture was vacuum-flushed with argon (3×)
  2. customplaced in 100° C.
  3. customfor 5 minutes
  4. filtrationThe mixture was filtered through a plug of silica
  5. washeluted with ethylacetate
  6. concentrationconcentrated
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-30aa918407dc4921b7b06b0118f6cbb1
Source dataset
uspto-grants-2005_04
Patent number
US06878727B2

Reaction notes

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