Ethyl Acetate → ((3-((1R)-1-(N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl)phenyl)methyl)carbamic acid tert-butyl ester

HRID 650827Notes

Reaction equation

HRID 650827 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=1)[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=NC2N(O)N=NC=2C=1.[NH2:29][C@H:30]([CH2:47][C:48]1[CH:57]=[CH:56][C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=1)[C:31]([N:33]([CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[O:43][CH2:44][CH2:45][OH:46])[CH3:34])=[O:32].C(OCC)(=O)C>CN(C)C=O.ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:12]([C:13](=[O:15])[NH:29][C@@H:30]([C:31](=[O:32])[N:33]([CH2:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[O:43][CH2:44][CH2:45][OH:46])[CH3:34])[CH2:47][C:48]2[CH:57]=[CH:56][C:55]3[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=3)[CH:49]=2)[CH:11]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 181649HOAtHCID 27559293-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 21310217(2R)-2-amino-N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methyl-3-(2-naphthyl)propionamide

Product 1

HCID 53653382((3-((1R)-1-(N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl)phenyl)methyl)carbamic acid tert-butyl esterYield 74.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-(tert-Butoxycarbonylaminomethyl)benzoic acid (113 mg, 0.45 mmol) and 7-aza-1-hydroxybenzotriazole (61 mg, 0.45 mmol) were dissolved in N,N-dimethylformamide (1 ml) and dichloromethane (1 ml). The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodilmide hydrochloride (86 mg, 0.45 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of (2R)-2-amino-N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methyl-3-(2naphthyl)propionamide (175 mg, 0.45 mmol) and ethylduisopropylamine (0.08 ml, 0.45 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted %With ethyl acetate (50 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (50 ml). The aqueous phase was extracted with ethyl acetate (2×15 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (40 g), using ethyl acetate/heptane 3:1 as eluent, to give 211 mg of ((3-((1R)-1-(N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl)phenyl)methyl)carbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with a 10% aqueous solution of sodium hydrogen sulfate (50 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×15 ml)
  5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (40 g)

Sources & evidence

ORD record
ord-d73318f4a7d945c0a8f682085b5beeb6
Source dataset
uspto-grants-2001_08
Patent number
US06274584B1

Reaction notes

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