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

HRID 1615812Notes

Reaction equation

HRID 1615812 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.[OH:24]S(O)(=O)=O>O>[OH:24][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

5

Reactant 3

HCID 1118Sulfuric AcidHCID 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 1

HCID 962WaterSolvent

Procedure

A solution of sodium nitrite (275 mg, 3.98 mmol) in water (1.6 mL) was slowly added to a cooled mixture of (R)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (1 g, 3.98 mmol, described in Intermediate 3) in of 10% aqueous H2SO4 (8 mL) at 0° C. The ice bath was removed and the reaction allowed to stir at ambient temperature. The reaction mixture was then placed into a 70° C. oil bath and the bath was heated to 100° C. Bubbling was observed and heating was continued until LCMS indicated that the reaction was complete. The reaction was slowly neutralized by addition of 30% NH4OH (ca. 2 mL) and the precipitate was collected by filtration and washed with water. The solid was then air dried and chromatographed by first mixing with silica and dry loading on a silica gel column. The product was eluted. with (10% MeOH/CH2Cl2). Concentration of the product containing fractions gave the title compound. MS: m/z=253 (M+1).

Workup

  1. customThe ice bath was removed
  2. customwas then placed into a 70° C.
  3. temperaturethe bath was heated to 100° C
  4. customBubbling
  5. temperatureheating
  6. additionThe reaction was slowly neutralized by addition of 30% NH4OH (ca. 2 mL)
  7. filtrationthe precipitate was collected by filtration
  8. washwashed with water
  9. customair dried
  10. customchromatographed
  11. additionby first mixing with silica
  12. customdry loading on a silica gel column
  13. washThe product was eluted
  14. additionConcentration of the product containing fractions

Sources & evidence

ORD record
ord-fc4dbe978b2a4b3cbeec76b63a8ff28e
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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