HCID 86618263, compound → HCID 68712999, compound

HRID 1159867Notes

Reaction equation

HRID 1159867 reaction equation
[F:1][C:2]1[C:3]([OH:22])=[C:4]([CH:20]=[O:21])[C:5]2[CH:6]=[CH:7][N:8]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:9]=2[CH:10]=1.[CH3:23][Mg+].[Br-]>C1COCC1.C1(C)C=CC=CC=1.C1COCC1>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([CH:20]([OH:21])[CH3:23])[C:3]=1[OH:22]

Participants

5

Reactant 2

HCID 86618263HCID 86618263, compound2×HCID 178418689HCID 178418689, compound

Product 1

HCID 68712999HCID 68712999, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

A solution of crude 6-fluoro-5-hydroxy-1-(phenylsulfonyl)-1H-indole-4-carbaldehyde (86.4 mg, 271 μmol; Intermediate 96) in THF (3 mL) was treated with MeMgBr (774 μL of a 1.4 M solution in Toluene/THF, 4 eq) at rt and stirred for 30 min. After 30 min another 2 eq and after 45 min another 4 eq. of Grignard solution were added and stirring continued for 15 min. The reaction mixture was quenched with sat. NH4Cl, extracted with EtOAc (3×), the combined org. phases washed with brine, dried and the solvent removed in vacuo to give a yellow-brownish solid (95.6 mg). This material was purified by prep. HPLC (15-45% MeCN/50 mM NH4HCO3) to yield the title compound as an yellowish solid (31.8 mg, 11% over 3 steps). MS (ESI+) for C16H14FNO4S m/z 318 (M-OH)+, 358 (M+Na)+.

Workup

  1. waitAfter 30 min another 2 eq
  2. additionafter 45 min another 4 eq. of Grignard solution were added
  3. stirringstirring
  4. waitcontinued for 15 min
  5. customThe reaction mixture was quenched with sat. NH4Cl
  6. extractionextracted with EtOAc (3×)
  7. washphases washed with brine
  8. customdried
  9. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-f8aab3845d7e4af7a22f0d0052193bd3
Source dataset
uspto-grants-2010_10
Patent number
US07812017B2

Reaction notes

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