Ammonium Chloride → HCID 22273648, compound

HRID 408391Notes

Reaction equation

HRID 408391 reaction equation
C([Li])(CC)C.[F:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[N:13]([Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[CH:14]=[CH:15][C:8]=12.CC1(C)[C@@]23C4(ON4S(=O)(=[O:34])C2)C[C@@H]1CC3.[Cl-].[NH4+]>C1COCC1.O.C(#N)C>[F:6][C:7]1[C:12]([OH:34])=[CH:11][N:10]=[C:9]2[N:13]([Si:16]([CH:20]([CH3:22])[CH3:21])([CH:23]([CH3:25])[CH3:24])[CH:17]([CH3:18])[CH3:19])[CH:14]=[CH:15][C:8]=12

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 112663344-Fluoro-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 16212266HCID 16212266, compoundHCID 178418400CID 53628100

Product 1

HCID 22273648HCID 22273648, compoundYield 49.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

sec-Butyllithium (27 mL, 38 mmol; 1.4M in cyclohexane) was added dropwise to 4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (5.0 g, 17 mmol; Example 1, Step D) in THF (200 mL) at −78° C., and the reaction was stirred for 30 minutes. (1S)-(+)-(10-Camphorsulfonyl)oxaziridine (9.4 g, 41 mmol) in THF (40 mL) was added rapidly, and the reaction was stirred at −78° C. for 30 minutes. A solution of saturated ammonium chloride (50 mL) was added, and the reaction mixture was allowed to reach room temperature. After one hour, the aqueous phase was extracted with AcOEt, dried over MgSO4 and concentrated to a solid, which was triturated in ether. The solid (most of the camphor side product) was filtered off, and the filtrate was concentrated and purified by reverse phase chromatography (Biotage SP4, C-18 40M+, water/ACN 40/60→0/100, 12 CV) to yield 4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-5-ol (2.6 g, 49% yield) as a paste.

Workup

  1. stirringthe reaction was stirred at −78° C. for 30 minutes
  2. customto reach room temperature
  3. waitAfter one hour
  4. extractionthe aqueous phase was extracted with AcOEt
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to a solid, which
  7. customwas triturated in ether
  8. filtrationThe solid (most of the camphor side product) was filtered off
  9. concentrationthe filtrate was concentrated
  10. custompurified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-d7ae48f9d59d4f25a247ee18bd7863b4
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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