Ammonia → HCID 58026166, compound

HRID 2387321Notes

Reaction equation

HRID 2387321 reaction equation
[CH3:1][C:2]([C:21]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:22]=1[C:23](O)=[O:24])([CH3:20])[CH2:3][C@:4]([O:12][Si:13]([CH2:18][CH3:19])([CH2:16][CH3:17])[CH2:14][CH3:15])([C:8]([F:11])([F:10])[F:9])[CH2:5][C:6]#[CH:7].[N:31]1C=CC=CC=1.S(Cl)(Cl)=O.N>C(Cl)Cl>[CH3:1][C:2]([C:21]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:22]=1[C:23]([NH2:31])=[O:24])([CH3:20])[CH2:3][C@:4]([O:12][Si:13]([CH2:18][CH3:19])([CH2:16][CH3:17])[CH2:14][CH3:15])([C:8]([F:11])([F:10])[F:9])[CH2:5][C:6]#[CH:7]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 1049PyridineHCID 24386Thionyl ChlorideHCID 58026139HCID 58026139, compound

Product 1

HCID 58026166HCID 58026166, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 14.2 g of 2-((S)-1,1-dimethyl-3-triethylsilanyloxy-3-trifluoromethylhex-5-ynyl)-5-fluorobenzoic acid (0.030 mol) in 400 mL of DCM was added 4.6 mL of pyridine (0.057 mol) followed by 3.3 mL of thionyl chloride (0.045 mol). The reaction was stirred for 25 minutes then carried on to next step. The crude acid chloride was cannulated into a flask containing ammonia (7 M in MeOH, 185 mL, 1.30 mol). The mixture was stirred for 40 minutes then quenched with saturated aqueous sodium bicarbonate solution. The mixture was then diluted with 20 mL of ethyl acetate, washed with two 100 mL portions of saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude mixture was chromatographed on silica gel using 0-50% ethyl acetate/hexanes to afford 7.1 g (50%) of 2-((S)-1,1-dimethyl-3-triethylsilanyloxy-3-trifluoromethylhex-5-ynyl)-5-fluorobenzamide.

Workup

  1. stirringThe mixture was stirred for 40 minutes
  2. customthen quenched with saturated aqueous sodium bicarbonate solution
  3. additionThe mixture was then diluted with 20 mL of ethyl acetate
  4. washwashed with two 100 mL portions of saturated aqueous sodium bicarbonate solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude mixture was chromatographed on silica gel using 0-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-966fec0bff4241b6ae2119a3c124858e
Source dataset
uspto-grants-2012_09
Patent number
US08268859B2

Reaction notes

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