Sulfuric Acid → HCID 178469183, compound

HRID 1912597Notes

Reaction equation

HRID 1912597 reaction equation
N[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]2[N:14]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[C:20]([F:25])[CH:19]=3)[CH:15]=[CH:16][C:3]=12.S(=O)(=O)(O)[OH:27].N([O-])=O.[Na+]>O1CCOCC1.O>[F:25][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[F:24])[CH2:17][N:14]1[C:4]2=[N:5][C:6]([CH3:13])=[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:2]([OH:27])=[C:3]2[CH:16]=[CH:15]1

Participants

6

Reactant 3

HCID 1118Sulfuric AcidHCID 23668193Sodium Nitrite2×HCID 71209202HCID 71209202, compound

Product 1

HCID 178469183HCID 178469183, compoundYield 93.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent4×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To solution of ethyl 4-amino-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (6 g, 14.8 mmol) in 1,4-dioxane (16 mL) at 0° C. was added dropwise a cold solution of sulfuric acid (16 mL, 300 mmol) in water (24 mL) followed by dropwise addition of a solution of sodium nitrite (4.2 g, 60.5 mmol) in water (12 mL) in 10 min. After stirring for 1 h at 0° C. and 3 h at RT for 3 h the mixture was cooled to 0° C. and more sodium nitrite (1.3 g) in water (3 mL) was added. After 2 h at RT cold water was added and the mixture was filtered washing with water. The solid was dissolved in MeOH and solid NaHCO3 was added. The mixture was stirred for 10 min then filtered and concentrated. The residue was dissolved in EtOAc and washed with saturated NaHCO3/water and the organic phase was dried (Na2SO4), concentrated and dried in vacuo to provide ethyl 1-(3,4-difluorobenzyl)-4-hydroxy-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (5.02 g, 13.8 mmol, 93% yield) as a brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.48 (t, J=7 Hz, 3 H), 2.86 (s, 3 H) 4.49 (q, J=7 Hz, 2 H), 5.40 (br s, 2 H), 6.66 (d, J=3.51 Hz, 1 H), 6.91-7.15 (m, 4 H), 12.82 (br s, 1 H); LCMS (m/z) ES+=347 (M+1).

Workup

  1. temperaturewas cooled to 0° C.
  2. filtrationthe mixture was filtered
  3. washwashing with water
  4. dissolutionThe solid was dissolved in MeOH
  5. additionsolid NaHCO3 was added
  6. stirringThe mixture was stirred for 10 min
  7. filtrationthen filtered
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in EtOAc
  10. washwashed with saturated NaHCO3/water
  11. dry with materialthe organic phase was dried (Na2SO4)
  12. concentrationconcentrated
  13. customdried in vacuo

Sources & evidence

ORD record
ord-79c2bc37b78146e3bdffd2f907d880e3
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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