Water → HCID 68281913, compound

HRID 2278605Notes

Reaction equation

HRID 2278605 reaction equation
N1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.CN(C)[CH2:10][CH2:11][CH2:12]N=C=NCC.[CH:19]([CH:22]1[CH2:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23]1)([CH3:21])[CH3:20].[OH2:31].C([O:35][CH2:36][CH3:37])(=O)C>CN(C)C=O>[CH2:36]([O:35][C@H:11]([CH3:10])[C:12]([N:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:30][CH:22]1[CH:19]([CH3:21])[CH3:20])=[O:31])[C:37]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 962WaterHCID 1049PyridineHCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 20766264HCID 20766264, compound

Product 1

HCID 68281913HCID 68281913, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3.9 ml of pyridine and 6.15 g of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 4.36 g of o-benzyl-D-lactic acid in 17 ml of N,N-dimethylformamide under argon. The reaction mixture is stirred at ambient temperature for 15 minutes, and then a solution of 3.9 g of (±)-2-isopropylindoline in 3 ml of N,N-dimethylformamide is added. The reaction mixture is stirred at ambient temperature for 16 hours and is then poured into a mixture of 100 ml of water and 80 ml of ethyl acetate and separated by settling out. The organic phase is separated and the aqueous phase is extracted with 2×80 ml of ethyl acetate. The organic phases are combined, washed with 60 ml of water, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 400 g cartridge of 15-40 μm silica, elution being carried out with pure heptane, and then with a 95/5 v/v heptane/ethyl acetate mixture, at a flow rate of 100 ml/min. 3.20 g of (R)-2-benzyloxy-1-(2-isopropyl-2,3-dihydroindol-1-yl)propan-1-one diastereoisomer (1) are thus obtained in the form of a very pale yellow oil, the characteristics of which are the following:

Workup

  1. stirringThe reaction mixture is stirred at ambient temperature for 16 hours
  2. customseparated
  3. customThe organic phase is separated
  4. extractionthe aqueous phase is extracted with 2×80 ml of ethyl acetate
  5. washwashed with 60 ml of water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe residue is purified by chromatography on a 400 g cartridge of 15-40 μm silica, elution

Sources & evidence

ORD record
ord-ce6419d85871463ab442576348a80a6d
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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