Diisopropylethylamine → HCID 59314093, compound

HRID 1047912Notes

Reaction equation

HRID 1047912 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH3:16])[C:5]([O:11][CH:12]2[CH2:15][CH2:14][CH2:13]2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[CH2:17]([O:19][C:20]([C:22]1([NH2:31])[CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23]1)=[O:21])[CH3:18].CCN(C(C)C)C(C)C.CC(O)C.C(Cl)Cl>C(Cl)Cl>[CH2:17]([O:19][C:20]([C:22]1([NH:31][C:7](=[O:9])[C:6]2[CH:10]=[C:2]([Br:1])[CH:3]=[C:4]([CH3:16])[C:5]=2[O:11][CH:12]2[CH2:15][CH2:14][CH2:13]2)[CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23]1)=[O:21])[CH3:18]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10921653Ethyl 2-amino-2,3-dihydro-1H-indene-2-carboxylateHCID 21966342Isopropanol methylene chlorideHCID 59314362HCID 59314362, compound

Product 1

HCID 59314093HCID 59314093, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 100 mL round bottom flask which contains a stirring bar is charged with 2-cyclobutoxyl-3-methyl-5-bromo-benzoic acid 317 (695 mg, 2.44 mmol) and dry DCM (8 mL). Stirring is initiated. After dissolution is complete, HTBU (924 mg, 2.44 mmol) is added. After 5 min, 2-amino-indane-2-carboxylic acid ethyl ester (500 mg, 2.44 mmol) is added followed by DIPEA (1.1 mL, 6.1 mmol). The reaction is allowed to stir for 15 days. 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 separatory funnel and diluted with EtOAc (50 mL). The organic phase is washed consecutively with dilute aqueous HCl (3%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL), and then dried over MgSO4, filtered and evaporated in vacuo to give 1.42 g of light orange solid. This solid is dissolved in 10 mL of DCM. This material is purified utilizing an ISCO Companion with a 40 g cartridge of silica. The gradient is 10% EtOAc in heptanes over 3 column volumes followed by a linear gradient to 60% EtOAc in heptanes over 10 column volumes. 17 mL fractions of UV active eluent are collected. Fractions 4 through 9 are combined and evaporated in vacuo. This yields white solid material (0.8 g, 70%).

Workup

  1. customA 100 mL round bottom flask which contains
  2. dissolutionAfter dissolution
  3. additionHTBU (924 mg, 2.44 mmol) is added
  4. stirringto stir for 15 days
  5. customconsumption of the starting amine
  6. customThe contents of the reaction flask are transferred to a separatory funnel
  7. additiondiluted with EtOAc (50 mL)
  8. washThe organic phase is washed consecutively with dilute aqueous HCl (3%, 25 mL), saturated aqueous NaHCO3 (25 mL) and brine (25 mL)
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customto give 1.42 g of light orange solid
  13. customThis material is purified
  14. custom17 mL fractions of UV active eluent are collected
  15. customevaporated in vacuo

Sources & evidence

ORD record
ord-fb4fc5f2f9b24beeb42a3452f3a23fe7
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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