Acetic Acid → HCID 71233116, compound

HRID 2369976Notes

Reaction equation

HRID 2369976 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH:14]3[CH2:16][CH:11]2[C:12](=O)[CH2:13]3)=[CH:6][CH:5]=1)([O-:3])=[O:2].[O-]S([O-])(=O)=O.[Na+].[Na+].[C@@H:25]1([NH2:32])[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]1[NH2:31].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH:14]3[CH2:16][CH:11]2[C@@H:12]([NH:31][C@@H:26]2[CH2:27][CH2:28][CH2:29][CH2:30][C@H:25]2[NH2:32])[CH2:13]3)=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 24436Sodium SulfateHCID 438061,2-Diaminocyclohexane, trans-HCID 5049666Sodium triacetoxyborohydrideHCID 71226801HCID 71226801, compound

Product 1

HCID 71233116HCID 71233116, compoundYield 46.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a round bottom flask was added 2-(4-nitrophenyl)-2-azabicyclo[2.2.1]heptan-6-one (120 mg, 0.517 mmol), CH2Cl2 (3 mL) and Na2SO4 (5 gms). The reaction was purged with argon. Then (1R,2R)-cyclohexane-1,2-diamine (118 mg, 1.033 mmol) and acetic acid (0.592 mL, 10.33 mmol) were added to the reaction. The reaction was stirred at rt for 1 hr. Then sodium triacetoxyborohydride (548 mg, 2.58 mmol) was added to the reaction and the reaction was stirred at rt overnight. The reaction was diluted with CH2Cl2 (50 ml) and filtered. The filtrate was washed with NaOH (0.5N, 30 ml), water (30 ml) and saturated aqueous NaCl (30 ml). The organic layer was dried with MgSO4, filtered and concentrated. The residue was purified by RP prep-HPLC. Two isomers were separated from RP prep-HPLC. The fractions with desired product, which eluted later than the undesired isomer, were concentrated to give (1R,2R)—N1-((6S)-2-(4-nitrophenyl)-2-azabicyclo[2.2.1]heptan-6-yl)cyclohexane-1,2-diamine (80 mg, 0.242 mmol, 46% yield) as a yellow solid. Anal. Calcd. for C18H26N4O2 m/z 330.4, found: 331.3 (M+H)+.

Workup

  1. customThe reaction was purged with argon
  2. stirringthe reaction was stirred at rt overnight
  3. filtrationfiltered
  4. washThe filtrate was washed with NaOH (0.5N, 30 ml), water (30 ml) and saturated aqueous NaCl (30 ml)
  5. dry with materialThe organic layer was dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by RP prep-HPLC
  9. customTwo isomers were separated from RP prep-HPLC
  10. washThe fractions with desired product, which eluted later than the undesired isomer
  11. concentrationwere concentrated

Sources & evidence

ORD record
ord-70819fd1a7004ceaa5daaeacfc083d2d
Source dataset
uspto-grants-2014_04
Patent number
US08710049B2

Reaction notes

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