Hydrochloric Acid → HCID 178436723, compound

HRID 1192720Notes

Reaction equation

HRID 1192720 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:28]([O:30]C)=[O:29])[C:5]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)=[C:6](/[N:14]=[N:15]/[N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:7]=1[C:8]#[C:9][Si](C)(C)C.[OH-].[Na+].O.Cl>O1CCCC1.CO.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:28]([OH:30])=[O:29])[C:5]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)=[C:6](/[N:14]=[N:15]/[N:16]2[CH2:17][CH2:18][CH2:19][CH2:20]2)[C:7]=1[C:8]#[CH:9]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962Water2×HCID 14798Sodium HydroxideHCID 178498036HCID 178498036, compound

Product 1

HCID 178436723HCID 178436723, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution of methyl 4-chloro-3′-fluoro-6-[(E)-pyrrolidin-1-yldiazenyl]-5-[(trimethylsilyl)ethynyl]biphenyl-2-carboxylate (1.0 kg, 2.2 mol) in tetrahydrofuran (3 L) and methanol (0.86 L) was treated with 2.0 M sodium hydroxide in water (3.4 L, 6.7 mol) and heated to 60° C. in 30 minutes and kept at an internal temperature of 60-63° C. for 90 minutes. The reaction mixture was cooled to 1 to 5° C. with an ice bath, treated with 3.0 M hydrogen chloride in water (2.8 L, 8.3 mol) in portions (temperature reached 16° C.) until the pH reached 1-2. The reaction mixture was diluted with ethyl acetate (2 L) and stirred for 20 minutes. The aqueous layer was separated and extracted with ethyl acetate (1 L). The combined organic layers were washed with water (2×3 L) and brine (300 mL), dried over sodium sulfate, filtered, and concentrated to give the desired product as an oil. This material was azeotroped with toluene (1 L) to give the desired product (theoretical yield 830 g) as a dark syrup. This material was used in the next step without further purification.

Workup

  1. temperatureThe reaction mixture was cooled to 1 to 5° C. with an ice bath
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (1 L)
  4. washThe combined organic layers were washed with water (2×3 L) and brine (300 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f73197db550348d7a947490b5277e51c
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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