Dimethylformamide → HCID 59272318, compound

HRID 1970274Notes

Reaction equation

HRID 1970274 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)=[CH:9][CH:10]=3)[C@@:5]3([CH2:26][O:25][C:24]([NH2:27])=[N:23]3)[C:4]=2[CH:3]=1.[CH3:28][C:29]([CH3:33])([CH3:32])[C:30]#[CH:31].CN(C=O)C.C(NC(C)C)(C)C>O.CO.C(Cl)Cl.[OH-].[NH4+].[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH3:28][C:29]([CH3:33])([CH3:32])[C:30]#[C:31][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)=[CH:9][CH:10]=3)[C@@:5]3([CH2:26][O:25][C:24]([NH2:27])=[N:23]3)[C:4]=2[CH:3]=1

Participants

12

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 135123,3-Dimethyl-1-butyneHCID 67246884HCID 67246884, compound

Product 1

HCID 59272318HCID 59272318, compoundYield 64.3%

Reagents, catalysts & solvents 7

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
90 °C

Procedure

(4S)-2′-Bromo-7′-(2-pyridinyloxy)spiro[1,3-oxazole-4,9′-xanthen]-2-amine (380 mg, 0.896 mmol), copper(i) iodide (34.1 mg, 0.179 mmol), tetrakis(triphenylphosphine)palladium (104 mg, 0.090 mmol), 3,3-dimethylbut-1-yne (221 mg, 2.69 mmol) and DMF (3583 μL, 0.896 mmol) were combined in a sealable tube. The reaction vessel was flushed with argon then di-isopropyl amine (3766 μL, 26.9 mmol) was added and the vessel was sealed and heated at 90° C. for 2 hours. The reaction was diluted with water (50 mL) and poured into a separatory funnel containing ethyl acetate (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water and then brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown foam that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to (4R)-2′-(3,3-dimethyl-1-butyn-1-yl)-7′-(2-pyridinyloxy)spiro[1,3-oxazole-4,9′-xanthen]-2-amine (245 mg, 0.576 mmol, 64.3% yield) as a light yellow solid. MS m/z=426.2 [M+H]+. Calc'd for C26H24N3O3: 426.2.

Workup

  1. customThe reaction vessel was flushed with argon
  2. customthe vessel was sealed
  3. additionpoured into a separatory funnel
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  6. washThe combined organic layers were washed with water
  7. dry with materialbrine, dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto provide a brown foam that

Sources & evidence

ORD record
ord-c4ef6e233fe64216a467b3153e630981
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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