2-(Trifluoromethyl)benzoyl chloride → HCID 59314376, compound

HRID 1047918Notes

Reaction equation

HRID 1047918 reaction equation
[NH2:1][C:2]1([C:11]([OH:13])=[O:12])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1.[CH3:14][CH2:15]N(C(C)C)C(C)C.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](Cl)=[O:28].CC(O)C.C(Cl)Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:14]([O:12][C:11]([C:2]1([NH:1][C:27](=[O:28])[C:26]2[CH:30]=[CH:31][CH:32]=[CH:33][C:25]=2[C:24]([F:35])([F:34])[F:23])[CH2:3][C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:10]1)=[O:13])[CH3:15]

Participants

7

Reactant 4

HCID 675612-(Trifluoromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 2509362-Aminoindane-2-carboxylic acidHCID 21966342Isopropanol methylene chloride

Product 1

HCID 59314376HCID 59314376, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A 30 mL vial is charged with 2-aminoindan-2-carboxylic acid (450 mg, 2.19 mmol) and dry DCM (5 mL). A stirring bar is added and stirring is initiated. DIPEA (0.61 mL, 3.51 mmol) is added. 2-(trifluoromethyl)-benzoyl chloride (388 μL, 2.63 mmol) and DMAP (3 mg, cat.) are added. The reaction is capped. After 38 days, tlc analysis (silica, 10% iPrOH/DCM) indicates that the starting is completely consumed. The contents of the reaction flask are transferred to a reparatory funnel and diluted with EtOAc (60 mL). The organic phase is washed with dilute aqueous HCl (2×25 mL), saturated aqueous NaHCO3 (2×25 mL), and brine (25 mL), dried over MgSO4, filtered and evaporated by pumping to constant weight yields 0.84 g of light orange solid. This is diluted with DCM and applied to a silica column ((24 g) on an ISCO Companion. 14 mL fractions of UV positive eluent are collected. Fraction 4-10 are combined and evaporated by pumping to constant weight to give light yellow solid (0.76 g, 92%).

Workup

  1. additionA stirring bar is added
  2. customThe reaction is capped
  3. customis completely consumed
  4. customThe contents of the reaction flask are transferred to a reparatory funnel
  5. additiondiluted with EtOAc (60 mL)
  6. washThe organic phase is washed with dilute aqueous HCl (2×25 mL), saturated aqueous NaHCO3 (2×25 mL), and brine (25 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customyields 0.84 g of light orange solid
  11. custom14 mL fractions of UV positive eluent are collected
  12. customevaporated

Sources & evidence

ORD record
ord-79805789a26540edab2247f038bb3b4a
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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