Diisopropylethylamine → 2-(2-Cyclobutoxy-3-methyl-benzoylamino)-4,5-dichloro-indan-2-carboxylic acid ethyl ester

HRID 1047873Notes

Reaction equation

HRID 1047873 reaction equation
[CH:1]1([O:5][C:6]2[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][C:7]=2[C:8]([OH:10])=O)[CH2:4][CH2:3][CH2:2]1.[CH2:16]([O:18][C:19]([C:21]1([NH2:32])[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([Cl:31])[C:27]=2[Cl:30])[CH2:22]1)=[O:20])[CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:16]([O:18][C:19]([C:21]1([NH:32][C:8](=[O:10])[C:7]2[CH:11]=[CH:12][CH:13]=[C:14]([CH3:15])[C:6]=2[O:5][CH:1]2[CH2:2][CH2:3][CH2:4]2)[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([Cl:31])[C:27]=2[Cl:30])[CH2:22]1)=[O:20])[CH3:17]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 593141552-Cyclobutyloxy-3-methylbenzoic acidHCID 685903502-Amino-4,5-dichloro-indan-2-carboxylic acid ethyl ester

Product 1

HCID 685899192-(2-Cyclobutoxy-3-methyl-benzoylamino)-4,5-dichloro-indan-2-carboxylic acid ethyl esterYield 76,529.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-cyclobutoxy-3-methyl-benzoic acid (225 mg, 1.1 mmol), 2-amino-4,5-dichloro-indan-2-carboxylic acid ethyl ester (254) (360 mg, 1.3 μmol), HATU 622 mg, 1.64 mmol) in anhydrous DMF (10 mL) is added DIPEA (360 μL, 2.20 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is suspended in H2O (50 mL) and washed with EtOAc (3×50 mL). Organics are combined and washed successively with NaHCO3 and brine, and then the organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (12 g silica gel, gradient elution: 0%-20% EtOAc in heptane) to give a pure product (255) as white powder (460 mg, 90%).

Workup

  1. customAfter the removal of DMF in vacuo
  2. washwashed with EtOAc (3×50 mL)
  3. washwashed successively with NaHCO3 and brine
  4. dry with materialthe organic layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash column chromatography (12 g silica gel, gradient elution: 0%-20% EtOAc in heptane)

Sources & evidence

ORD record
ord-42ebbcaab35349438b723dac694c377c
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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