2-Acetoxy-m-toluic acid → HCID 59314302, compound

HRID 1047828Notes

Reaction equation

HRID 1047828 reaction equation
[O:1]([C:5]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)[C:2]([CH3:4])=[O:3].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:39]([O:41][C:42]([C:44]1([NH2:53])[CH2:52][C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH2:45]1)=[O:43])[CH3:40].CCN(C(C)C)C(C)C>CC(O)C.C(Cl)Cl.C(Cl)Cl>[CH2:39]([O:41][C:42]([C:44]1([NH:53][C:7](=[O:9])[C:6]2[CH:10]=[CH:11][CH:12]=[C:13]([CH3:14])[C:5]=2[O:1][C:2](=[O:3])[CH3:4])[CH2:52][C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH2:45]1)=[O:43])[CH3:40]

Participants

7

Reactant 4

HCID 780942-Acetoxy-m-toluic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylate

Product 1

HCID 59314302HCID 59314302, compoundYield 161.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21966342Isopropanol methylene chlorideSolvent

Procedure

A 40 mL vial containing a stirring bar is charged with 2-acetoxyl-3-methyl-benzoic acid (1 g, 4.87 mmol) and dry DCM (14 mL), and stirring is initiated. After dissolution is complete, HBTU (1.85 g, 4.87 mmoles) is added. After 5 min, 2-amino-indane-2-carboxylic acid ethyl ester (1 g, 4.87 mmol) is added followed by DIPEA (2.1 mL, 12.18 mmol). The reaction is allowed to stir for 110 h. Analysis by tlc of the reaction mixture (silica, 5% iPrOH/DCM) indicates complete consumption of the starting amine. The contents of the reaction flask are transferred to a reparatory funnel and diluted with EtOAc (100 mL). This is washed consecutively with dilute aqueous HCl (3%, 40 mL), saturated aqueous NaHCO3 (50 mL) and brine (50 mL), dried over MgSO4, filtered and evaporated in vacuo to provide 3 g of a light orange solid. This material is dissolved in 15 mL of DCM. This material is purified utilizing an ISCO Companion with an 80 g cartridge of silica. The gradient is 10% EtOAc in heptanes over 3 column volumes followed by a linear gradient to 50% EtOAc over 12 column volumes. Fractions 19 through 27 are combined and evaporated in vacuo to give 1.38 g of white solid.

Workup

  1. additionA 40 mL vial containing a stirring bar
  2. dissolutionAfter dissolution
  3. stirringto stir for 110 h
  4. customconsumption of the starting amine
  5. customThe contents of the reaction flask are transferred to a reparatory funnel
  6. additiondiluted with EtOAc (100 mL)
  7. washThis is washed consecutively with dilute aqueous HCl (3%, 40 mL), saturated aqueous NaHCO3 (50 mL) and brine (50 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-29d155add5334b6fbbb28a7df890d3ad
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

Loading…