Ammonium Chloride → HCID 22273648, compound

HRID 79583Notes

Reaction equation

HRID 79583 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>[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

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 112663344-Fluoro-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridineHCID 16212283(1R,8R)-11,11-dimethyl-5-oxa-3lambda6-thia-4-azatetracyclo[6.2.1.01,6.04,6]undecane 3,3-dioxideHCID 178418400CID 53628100

Product 1

HCID 22273648HCID 22273648, compoundYield 51.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

sec-Butyl lithium (8.06 mL, 11.3 mmol, 1.4 M in cyclohexane) was added dropwise to 4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (1.5 g, 5.13 mmol, prepared as described in L′Heureux, et al., Org. Lett., 5(26) p. 5023 (2003)) in THF (100 mL) at −78° C. The reaction was stirred for 30 minutes. (1R)-(−)-(10-camphorsulfonyl)oxaziridine (2.94 g, 12.8 mmol) in THF (10 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 concentrated and purified by chromatography (25M, toluene/AcOEt 95/5) to yield a paste. The paste was triturated with hexanes, and the filtrate was concentrated to dryness to yield 4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-5-ol (820 mg, 51.8% yield) as an oil, which solidified upon standing.

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 concentrated
  10. custompurified by chromatography (25M, toluene/AcOEt 95/5)
  11. customto yield a paste
  12. customThe paste was triturated with hexanes
  13. concentrationthe filtrate was concentrated to dryness

Sources & evidence

ORD record
ord-9f9fa1265c5e4653ba80625caf68338a
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

Loading…