Sodium Hydroxide → HCID 67229538, compound

HRID 2067846Notes

Reaction equation

HRID 2067846 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][C@@:4]([C:11]([N:13]2[CH2:18][C@@H:17]3[CH2:19][C@H:14]2[CH2:15][N:16]3[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:12])([CH2:7][CH:8]([F:10])[F:9])[CH2:3]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:41][O:42][C@H:43]1[C:48](=O)[CH2:47][CH2:46][O:45][CH2:44]1.[OH-].[Na+]>ClCCl.O>[C:23]([O:22][C:20]([N:16]1[CH2:15][C@@H:14]2[CH2:19][C@H:17]1[CH2:18][N:13]2[C:11]([C@@:4]1([CH2:7][CH:8]([F:9])[F:10])[CH2:5][CH2:6][C@@H:2]([NH:1][C@@H:48]2[C@H:43]([O:42][CH3:41])[CH2:44][O:45][CH2:46][CH2:47]2)[CH2:3]1)=[O:12])=[O:21])([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 11320949(R)-3-methoxydihydro-2H-pyran-4(3H)-oneHCID 67230182HCID 67230182, compound

Product 1

HCID 67229538HCID 67229538, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 0° C. solution of tert-butyl (1S,4S)-5-{[(1S,3R)-3-amino-1-(2,2-difluoroethyl)cyclopentyl]carbonyl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (3.45 g, 9.2 mmol) in dichloromethane (50 ml) was treated with sodium triacetoxyborohydride (5.34 g, 25.2 mmol) and (3R)-3-methoxytetrahydro-4H-pyran-4-one (2.31 g, 17.8 mmol). The reaction was stirred under nitrogen at 0° C. for 30 minutes then allowed to warm to room temperature and stirred for 47 hours. The reaction was treated with 2.5N NaOH (35 mL) and stirred for 10 minutes. The reaction was diluted with water and the layers separated. The aqueous layer was extracted twice with ethyl acetate. The dichloromethane layer was concentrated under reduced pressure and partitioned between ethyl acetate and water. The organic layers were combined, washed with brine, dried over MgSO4, concentrated under reduced pressure and purified with the Biotage (0-100% methanol/ethyl acetate, 15 column volumes) to give 1,5-anhydro-3-{[(1R,3S)-3-{[(1S,4S)-5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-3-(2,2-difluoroethyl)cyclopentyl]amino}-2,3-dideoxy-4-O-methyl-D-erythro-pentitol (2.13 g, 47%) which was used without further purification in the next step.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 47 hours
  3. stirringstirred for 10 minutes
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted twice with ethyl acetate
  6. concentrationThe dichloromethane layer was concentrated under reduced pressure
  7. custompartitioned between ethyl acetate and water
  8. washwashed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated under reduced pressure
  11. custompurified with the Biotage (0-100% methanol/ethyl acetate, 15 column volumes)

Sources & evidence

ORD record
ord-27d8688523474a55a9fa980be156d930
Source dataset
uspto-grants-2012_10
Patent number
US08293903B2

Reaction notes

Loading…