2-Methyl-3-butyn-2-ol → HCID 67387634, compound

HRID 335838Notes

Reaction equation

HRID 335838 reaction equation
[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:22]=1)[C:18]1[CH:17]=[C:16]([OH:19])[C:15]([F:20])=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8](Br)=[CH:9][CH:10]=1.[CH3:23][C:24]([OH:28])([C:26]#[CH:27])[CH3:25].[NH4+].[Cl-]>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.[Cu]I.CN(C=O)C>[NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:22]=1)[C:18]1[CH:17]=[C:16]([OH:19])[C:15]([F:20])=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([C:27]#[C:26][C:24]([OH:28])([CH3:25])[CH3:23])=[CH:9][CH:10]=1

Participants

7

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 25517Ammonium ChlorideHCID 58466191HCID 58466191, compound

Product 1

HCID 67387634HCID 67387634, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A vial charged with (S)-2-amino-7′-bromo-3′-fluoro-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (0.225 g, 0.616 mmol), Pd(PPh3)4 (0.071 g, 0.062 mmol), and copper(i) iodide (0.012 g, 0.062 mmol), was treated with 3 mL DMF followed by DIPA (1.317 mL, 9.24 mmol). The solution was purged with argon for 2 minutes then 2-methylbut-3-yn-2-ol (0.301 mL, 3.08 mmol) was added and the vial was sealed and heated to 80° C. overnight. The reaction mixture was poured into saturated NH4Cl (50 mL) and was extracted with EtOAc (3×25 mL). The combined organics were washed with brine, dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography [0-100% (9:1:0.1—CH2Cl2:MeOH:NH4OH)/CH2Cl2] provided (R)-2-amino-3′-fluoro-7′-(3-hydroxy-3-methylbut-1-ynyl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol. MS m/z=369.3 [M+H].

Workup

  1. customThe solution was purged with argon for 2 minutes
  2. customthe vial was sealed
  3. extractionwas extracted with EtOAc (3×25 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customPurification of the crude residue by column chromatography [0-100% (9:1:0.1—CH2Cl2:MeOH:NH4OH)/CH2Cl2]

Sources & evidence

ORD record
ord-f65b247a5164497089dc304f60200542
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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