Diisopropylethylamine → (R)-Methyl 3-(2-tert-butylbenzamido)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1193270Notes

Reaction equation

HRID 1193270 reaction equation
[C:1]([C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)([CH3:4])([CH3:3])[CH3:2].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.[NH2:47][C@H:48]1[C:56]2[C:51](=[CH:52][CH:53]=[C:54]([C:57]([O:59][CH3:60])=[O:58])[CH:55]=2)[CH2:50][CH2:49]1>ClCCl>[C:1]([C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([NH:47][C@H:48]1[C:56]2[C:51](=[CH:52][CH:53]=[C:54]([C:57]([O:59][CH3:60])=[O:58])[CH:55]=2)[CH2:50][CH2:49]1)=[O:9])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 136850tert-Butylbenzoic acid (mixed isomers)HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 55278060(R)-Methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate

Product 1

HCID 66798706(R)-Methyl 3-(2-tert-butylbenzamido)-2,3-dihydro-1H-indene-5-carboxylateYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

2-tert-Butylbenzoic acid (0.75 g, 4.2 mmol, 1 eq) was dissolved in dichloromethane (40 ml), and at 0° C. HATU (1.5 g, 4.2 mmol, 1 eq) and DIPEA (1.7 ml, 10.52 mmol, 2.5 eq) were added and stirring was carried out for 30 min. Then (R)-methyl 3-amino-2,3-dihydro-1H-indene-5-carboxylate (A-07) (804 mg, 4.2 mmol, 1 eq) dissolved in dichloromethane (20 ml) was added and stirring was carried out for 16 h at RT. After monitoring by thin-layer chromatography, the reaction solution was diluted with dichloromethane (250 ml), washed with sat. sodium hydrogen carbonate solution (50 ml), sat. ammonium chloride solution (50 ml), water (50 ml) and sat. NaCl solution (50 ml), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 8-10% ethyl acetate in hexane). Yield: 57% (1.6 g, 4.56 mmol).

Workup

  1. customat 0° C
  2. additionwas added
  3. stirringstirring
  4. waitwas carried out for 16 h at RT
  5. washwashed with sat. sodium hydrogen carbonate solution (50 ml), sat. ammonium chloride solution (50 ml), water (50 ml) and sat. NaCl solution (50 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (silica gel, 8-10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-344a6695d6d44c0ba3250a4ec7f31347
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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