2-Chlorothiophene → HCID 11501812, compound

HRID 335507Notes

Reaction equation

HRID 335507 reaction equation
C[Si](C)(C)CC[O:5][C:6](=[O:29])[CH2:7][C:8]1[C:16]2[C:11](=[CH:12][C:13]([F:19])=[C:14]([O:17][CH3:18])[CH:15]=2)[N:10]([C:20]([C:22]2[S:23][C:24]([Cl:27])=[CH:25][CH:26]=2)=[O:21])[C:9]=1[CH3:28].ClC1SC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.[Cl-].[NH4+]>[Cl:27][C:24]1[S:23][C:22]([C:20]([N:10]2[C:11]3[C:16](=[CH:15][C:14]([O:17][CH3:18])=[C:13]([F:19])[CH:12]=3)[C:8]([CH2:7][C:6]([OH:29])=[O:5])=[C:9]2[CH3:28])=[O:21])=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 72992-ChlorothiopheneHCID 2724141Tetrabutylammonium FluorideHCID 131728960HCID 131728960, compound

Product 1

HCID 11501812HCID 11501812, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

A solution of the product from Step 3, 2trimethylsilylethyl-{1-[(5-chlorothien-2-yl)carbonyl]-6-fluoro-5-methoxy-2-methyl-1H-indol-3-yl}acetate 5, R1=H=B, R2=CH3, R3=F, R4=CH2CH2Si(CH3)3, A=5-chlorothiophene) (600 mg, 1.24 mmol) dissolved in 8 mL of THF was treated with, a solution of tetrabutylammonium fluoride (1M, 3.1 mL, 3.1 mmol) in THF. The solution was stirred at room temperature until the ester had been cleaved (ca. 1 hour), and then the solution was diluted with saturated aqueous ammonium chloride and extracted with ethyl acetate. The combined extracts were washed with brine, dried over MgSO4 and concentrated to give a solid that was purified by chromatography elating with hexanes and ethyl acetate to provide 280 mg, 59% of pure {1-[(5-chlorothien-2-yl)carbonyl]-6-fluoro-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid (6, R1=H, R2=CH3, R3=F, R4=H, A =5-chlorothiophene), mp 169° C. 1H NMR (CDCl3/300 MHz) 7.35 (d, 1H, J=4.0 Hz), 7.09 (d, 1H, J=11.7 Hz), 7.00 (d, 1H, J=7.2 Hz), 6.98 (d, 1H, J=4.0 Hz), 3.93 (s, 3H), 3.70 (s, 2H), 2.42 (s, 3H).

Workup

  1. custom(ca. 1 hour)
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto give a solid
  7. customthat was purified by chromatography

Sources & evidence

ORD record
ord-e327ffbc41694f75857cb5daed93c20d
Source dataset
uspto-grants-2014_11
Patent number
US08884020B2

Reaction notes

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