Methanol → HCID 58368604, compound

HRID 1192718Notes

Reaction equation

HRID 1192718 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:24]([O:26][CH3:27])=[O:25])[C:5]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:6]([N+:14]([O-])=O)[C:7]=1[C:8]#[C:9][Si:10]([CH3:13])([CH3:12])[CH3:11].CO.[Cl-].[NH4+].O>C(OCC)(=O)C.[Zn]>[NH2:14][C:6]1[C:7]([C:8]#[C:9][Si:10]([CH3:12])([CH3:11])[CH3:13])=[C:2]([Cl:1])[CH:3]=[C:4]([C:24]([O:26][CH3:27])=[O:25])[C:5]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 25517Ammonium ChlorideHCID 58368582HCID 58368582, compound

Product 1

HCID 58368604HCID 58368604, compoundYield 102.3%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 4-chloro-3′-fluoro-6-nitro-5-[(trimethylsilyl)ethynyl]biphenyl-2-carboxylate (330 g, 780 mmol) in ethyl acetate (1 L) was treated with methanol (1 L) and saturated aqueous ammonium chloride solution (670 mL, 10 mol). The mixture was cooled with an ice-water bath and treated with <10 micron zinc dust (310 g, 4.7 mol) in portions with internal temperature at 15 to 45° C. After addition, the ice bath was removed and the reaction mixture was stirred for 3 hours. The reaction mixture was filtered over a pad of celite and rinsed with ethyl acetate (2×1 L). The combined filtrate was diluted with brine (500 mL) and stirred for 10 minutes. The brine layer was separated and extracted with ethyl acetate (300 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give a green oil which contained approximately 12% water. This material was dried with azeotropic drying with toluene to give the desired product (300 g, quantitative) as a green semi-solid. HPLC 90.5% pure @ 220 nm. LCMS for C19H20ClFNO2Si (M+H)+: m/z=376.1; Found: 376.0; 1H NMR (300 MHz, DMSO-d6): δ 7.56-7.42 (m, 1H), 7.28-7.16 (m, 7.28-7.16 (m, 1 H), 7.07 (s, 1 H), 7.06-6.94 (m, 2 H), 5.06 (s, 2 H), 3.47 (s, 3 H), 0.25 (s, 9 H).

Workup

  1. temperatureThe mixture was cooled with an ice-water bath
  2. additionAfter addition
  3. customthe ice bath was removed
  4. filtrationThe reaction mixture was filtered over a pad of celite
  5. washrinsed with ethyl acetate (2×1 L)
  6. additionThe combined filtrate was diluted with brine (500 mL)
  7. stirringstirred for 10 minutes
  8. customThe brine layer was separated
  9. extractionextracted with ethyl acetate (300 mL)
  10. dry with materialThe combined organic layers were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a green oil which
  14. customThis material was dried
  15. dry with materialwith azeotropic drying with toluene

Sources & evidence

ORD record
ord-be2b15cd66f94e3cbaa7af6fc52a0ab7
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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