1,2-Dichloroethane → N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-hydroxy-5-(2-oxopyrrolidin-1-yl)-benzamide

HRID 1612475Notes

Reaction equation

HRID 1612475 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH:10]=1)[C:5]([OH:7])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:31][C:32]([CH3:53])([CH3:52])[CH2:33][CH2:34][NH:35][C:36](=[O:51])[C@H:37]([CH3:50])[CH2:38][C@H:39]([OH:49])[C@@H:40]([NH2:48])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>CN(C=O)C>[CH2:41]([C@H:40]([NH:48][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH:10]=[C:2]([OH:1])[CH:3]=1)[C@@H:39]([OH:49])[CH2:38][C@H:37]([C:36](=[O:51])[NH:35][CH2:34][CH2:33][C:32]([CH3:31])([CH3:52])[CH3:53])[CH3:50])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 222530273-Hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acidHCID 68890142(2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide2×

Product 1

HCID 10218066N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-hydroxy-5-(2-oxopyrrolidin-1-yl)-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acid (D6) (0.449 g, 2.03 mmol), EDC (0.389 g, 2.03 mmol) and HOBT (0.311 g, 2.03 mmol) in DMF (8 ml) was added (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)amide (D2(0.50 g, 1.56 mmol). After stirring for 20 hrs at room temperature, the DMF was evaporated and ethyl acetate and water were added. The product was extracted into ethyl acetate and the combined extracts were washed with 2N HCl, saturated aqueous sodium bicarbonate solution and brine and then dried over sodium sulfate and evaporated. Purification by column chromatography on silica gel (elution with 2–5% methanol in dichloromethane) gave the product, 0.588 g.

Workup

  1. customthe DMF was evaporated
  2. additionethyl acetate and water were added
  3. extractionThe product was extracted into ethyl acetate
  4. washthe combined extracts were washed with 2N HCl, saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customPurification by column chromatography on silica gel (elution with 2–5% methanol in dichloromethane)
  8. customgave the product, 0.588 g

Sources & evidence

ORD record
ord-f72a3c0bff74448e835f17e812e8e224
Source dataset
uspto-grants-2006_01
Patent number
US06992103B2

Reaction notes

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