Potassium Carbonate → (R)-Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(2-ethoxyethoxy)phenyl)propanoate

HRID 929946Notes

Reaction equation

HRID 929946 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]([O-])([O-])=O.[K+].[K+].Br[CH2:29][CH2:30][O:31][CH3:32]>C(#N)C.CC(OC)(C)C.[I-].[Na+]>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:29][CH2:30][O:31][CH2:32][CH3:22])=[CH:17][CH:16]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 7016055Boc-D-Tyr-OMe

Product 1

HCID 86718528(R)-Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(2-ethoxyethoxy)phenyl)propanoateYield 96.2%

Reagents, catalysts & solvents 3

HCID 5238Sodium IodideCatalystHCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a suspension of (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-hydroxyphenyl)-propanoate (4.43 g, 15.00 mmol), K2CO3 (4.15 g, 30.0 mmol) and sodium iodide (112 mg, 750 μmol) in acetonitrile (100 mL) was added 1-bromo-2-methoxyethane (5.64 mL, 60.0 mmol) and the resulting mixture was stirred at reflux for 2 days. The reaction mixture was diluted with TBME and washed with H2O and brine. Combined extracts were dried over MgSO4, filtered and concentrated to provide the title compound as a yellow oil (5.3 g, 95%). TLC (toluene/TBME 2:1) Rf=0.44; tR=1.084 min (UPLC 1); LC-MS: [M+H] 354; Rt 1.02 min; (LCMS method 2); 1H NMR (400 MHz, CDCl3): δ 7.05 (d, 2H), 6.88 (d, 2H), 4.96 (br d, 1H), 4.58 (m, 1H), 4.12 (dd, 2H), 3.76 (dd, 2H), 3.73 (s, 3H), 3.47 (s, 3H), 3.05 (m, 2H), 1.44 (s, 9H).

Workup

  1. temperatureat reflux for 2 days
  2. washwashed with H2O and brine
  3. dry with materialCombined extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-6b8ed6181a19445cbc1863cfba18d5e1
Source dataset
uspto-grants-2016_03
Patent number
US09296733B2

Reaction notes

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