Ammonium Hydroxide → (R)-5-Hydroxy-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 1038981Notes

Reaction equation

HRID 1038981 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:7]=[C:8]2[C:21](=[CH:22][CH:23]=1)[CH2:20][C@:10]1([C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[NH:12][C:11]1=[O:19])[CH2:9]2.[NH4+].[OH-:25]>O.OS(O)(=O)=O>[OH:25][C:6]1[CH:7]=[C:8]2[C:21](=[CH:22][CH:23]=1)[CH2:20][C@:10]1([C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[NH:12][C:11]1=[O:19])[CH2:9]2

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 23668193Sodium NitriteHCID 53260812(R)-5-Amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Product 1

HCID 58118679(R)-5-Hydroxy-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Procedure

A solution of sodium nitrite (275 mg, 3.98 mmol) in water (1.6 mL) was slowly added to a cooled mixture of (2R)-5-Amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (1.00 g, 3.98 mmol, Intermediate 1) in 10% H2SO4 (0.8 mL conc H2SO4+7.2 mL water) at 0° C. The ice bath was removed and the stirred reaction was allowed to warm to ambient temperature. The reaction was then placed into a 70° C. oil bath and heated to 100° C. Bubbling was observed and heating was continued until LCMS analysis showed a completed reaction. The reaction was slowly quenched/neutralized with concentrated aqueous NH4OH (about 2 mL) such that the pH was about 8 at the end of multiple sonication/heating cycles in order to produce a stable pH and a solid suitable for filtration. The solid was collected by filtration and washed with water. The solid was then air dried and chromatographed by first mixing with about twice the amount of silica and then dry loading on a silica gel column. The product was eluted with 10% MeOH/DCM. Pooling and concentration of the product containing fractions provided the title compound. MS: m/z=253 (M+1).

Workup

  1. customThe ice bath was removed
  2. customthe stirred reaction
  3. customwas then placed into a 70° C.
  4. temperatureheated to 100° C
  5. customBubbling
  6. temperatureheating
  7. customa completed reaction
  8. temperatureof multiple sonication/heating cycles in order
  9. customto produce a stable pH
  10. filtrationa solid suitable for filtration
  11. filtrationThe solid was collected by filtration
  12. washwashed with water
  13. customair dried
  14. customchromatographed
  15. additionby first mixing with about twice the amount of silica
  16. customdry loading on a silica gel column
  17. washThe product was eluted with 10% MeOH/DCM
  18. additionPooling and concentration of the product containing fractions

Sources & evidence

ORD record
ord-3e2937812d1449639c652053284f8e9f
Source dataset
uspto-grants-2013_10
Patent number
US08552023B2

Reaction notes

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