Ammonium Chloride → 2-tert-butoxycarbonyloxy-4-[3-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-hydroxy-prop-1-ynyl]-5-fluoro-indole-1-carboxylic acid tert-butyl ester

HRID 1860984Notes

Reaction equation

HRID 1860984 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12](I)[C:13]([F:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[O:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]([O:31][C:32]([N:34]1[CH:38]=[CH:37][CH:36]=[C:35]1[CH:39]([OH:42])[C:40]#[CH:41])=[O:33])([CH3:30])([CH3:29])[CH3:28].[Cl-].[NH4+]>C1COCC1.C(N(CC)CC)C.[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:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([C:41]#[C:40][CH:39]([C:35]3[N:34]([C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:33])[CH:38]=[CH:37][CH:36]=3)[OH:42])[C:13]([F:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[O:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 25517Ammonium ChlorideHCID 102058642-Tert-butoxycarbonyloxy-5-fluoro-4-iodo-indole-1-carboxylic acid tert-butyl esterHCID 112530122-(1-Hydroxy-prop-2-ynyl)-pyrrole-1-carboxylic acid tert-butyl ester

Product 1

HCID 102100552-tert-butoxycarbonyloxy-4-[3-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-hydroxy-prop-1-ynyl]-5-fluoro-indole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 2-tert-butoxycarbonyloxy-5-fluoro-4-iodo-indole-1-carboxylic acid tert-butyl ester (from Example 2 above) (9.85 g, 20.0 mmol), and 2-(1-hydroxy-prop-2-ynyl)-pyrrole-1-carboxylic acid tert-butyl ester (from Example 1 above) (7.96 g, 36.0 mmol) in dry THF (85 mL) and triethylamine (Aldrich, 85 mL) was degassed by bubbling argon through the solution for 15 minutes. At this time copper(I) iodide (0.61 g, 3.2 mmol) and (Ph3P)4Pd (Aldrich, 1.85 g, 1.6 mmol) were added, and the reaction mixture was stirred at room temperature for 3.5 hours. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution (100 mL) and extracted with ethyl acetate (3×150 mL). The combined organic extracts were successively washed with water (100 mL) and brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Biotage, 75-S, 9/1 hexanes/ethyl acetate) afforded 2-tert-butoxycarbonyloxy-4-[3-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-hydroxy-prop-1-ynyl]-5-fluoro-indole-1-carboxylic acid tert-butyl ester as a light orange amorphous solid. (Yield 9.5 g, 83%).

Workup

  1. customby bubbling argon through the solution for 15 minutes
  2. extractionextracted with ethyl acetate (3×150 mL)
  3. washThe combined organic extracts were successively washed with water (100 mL) and brine (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eac51d3022d9481c9c1a1f92295b8d07
Source dataset
uspto-grants-2003_03
Patent number
US06531598B1

Reaction notes

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