Sodium Azide → HCID 86622387, compound

HRID 1158373Notes

Reaction equation

HRID 1158373 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13]OS(C)(=O)=O)[C@H:10]([CH2:19][N:20]([CH:37]([CH3:39])[CH3:38])[C:21](=[O:36])[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH2:32][CH2:33][O:34][CH3:35])[CH:23]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:40]=[N+:41]=[N-:42].[Na+].C([O-])(O)=O.[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([CH2:19][N:20]([CH:37]([CH3:38])[CH3:39])[C:21](=[O:36])[C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH2:32][CH2:33][O:34][CH3:35])[CH:23]=2)[C@H:11]([CH2:13][N:40]=[N+:41]=[N-:42])[CH2:12]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 33557Sodium AzideHCID 516892Sodium BicarbonateHCID 59512307HCID 59512307, compound

Product 1

HCID 86622387HCID 86622387, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (3R,4S)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (2.7 g, 4.71 mmol) in DMF (20 mL) is added in one portion NaN3 (774 mg, 11.8 mmol) and the mixture is stirred at 70° C. overnight. After cooling to room temperature, a saturated aqueous NaHCO3 solution is added, followed by extraction with diethyl ether. The combined organics are washed with brine, dried over Na2SO4 and concentrated. The crude product is purified by RP-HPLC on a PrepC18 OBD column (dimensions: 30×100 mm; 5 μM particle size, SunFire Ltd) and using a 95-5% gradient of MeCN/H2O 5:95 (containing 0.1% TFA) to MeCN/H2O 95:5 (containing 0.1% TFA) over 20 min gives the title compound as colorless oil. TLC, Rf (hexane/AcOEt 1:3)=0.31. MS: 520.2 [M+H]+. tR (HPLC, Nucleosil C18HD column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 5.04 min.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionfollowed by extraction with diethyl ether
  3. washThe combined organics are washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product is purified by RP-HPLC on a PrepC18 OBD column (dimensions: 30×100 mm; 5 μM particle size, SunFire Ltd)
  7. customover 20 min

Sources & evidence

ORD record
ord-addcbe3518a94a35a58b6789c343a822
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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