Sodium Hydroxide → HCID 67229365, compound

HRID 2067840Notes

Reaction equation

HRID 2067840 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][C@@:4]([C:9]([N:11]2[CH2:16][C@@H:15]3[CH2:17][C@H:12]2[CH2:13][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:10])([CH2:7][CH3:8])[CH2:3]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:39][O:40][CH:41]1[C:46](=O)[CH2:45][CH2:44][O:43][CH2:42]1.[OH-].[Na+]>ClCCl.O>[CH2:7]([C@:4]1([C:9]([N:11]2[CH2:16][C@@H:15]3[CH2:17][C@H:12]2[CH2:13][N:14]3[C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])=[O:10])[CH2:5][CH2:6][C@@H:2]([NH:1][C@@H:46]2[CH2:45][CH2:44][O:43][CH2:42][C@H:41]2[O:40][CH3:39])[CH2:3]1)[CH3:8].[C:21]([O:20][C:18]([N:14]1[CH2:13][C@@H:12]2[CH2:17][C@H:15]1[CH2:16][N:11]2[C:9]([C@@:4]1([CH2:7][CH3:8])[CH2:5][CH2:6][C@@H:2]([NH:1][C@@H:46]2[C@H:41]([O:40][CH3:39])[CH2:42][O:43][CH2:44][CH2:45]2)[CH2:3]1)=[O:10])=[O:19])([CH3:23])([CH3:22])[CH3:24]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 235336103-Methoxyoxan-4-oneHCID 67228776HCID 67228776, compound

Product 2

HCID 67229365HCID 67229365, compoundHCID 67230290HCID 67230290, compound

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-ethylcyclopentyl]carbonyl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (1.58 g, 4.7 mmol) in dichloromethane (25 ml) was treated with sodium triacetoxyborohydride (2.36 g, 11.1 mmol) and 3R)-3-methoxytetrahydro-4H-pyran-4-one (0.76 g, 7.6 mmol). The reaction was stirred under nitrogen at 0° C. for 30 minutes then allowed to warm to room temperature and stirred for 15 hours. The reaction was treated with 2.5N NaOH (10 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 the desired product, 1,5-anhydro-3-{[(1R,3S)-3-{[(1S,4S)-5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-3-ethylcyclopentyl]amino}-2,3-dideoxy-4-O-methyl-D-erythro-pentitol. LC/MS (M+H)=452.3124 exp, 452.3135 obs; 1H NMR (400 MHz, CDCl3) δ ppm 4.94-4.41 (2H), 4.11-4.04 (1H), 3.97-3.91 (1H), 3.53-3.18 (11H), 2.83-2.75 (1H), 2.60-2.30 (1H), 2.03-1.55 (10H), 1.48-1.37 (11H), 0.85-0.78 (3H)

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 15 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-4e7b8ce983db4f29be72c9538c707cd7
Source dataset
uspto-grants-2012_10
Patent number
US08293903B2

Reaction notes

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