4-Fluorobenzaldehyde → methyl (1S,2R,3S,4R)-3-[(4-fluorobenzyl)amino]bicyclo[2.2.1]heptane-2-carboxylate

HRID 2408774Notes

Reaction equation

HRID 2408774 reaction equation
Cl.COC([C@H]1[C@@H](N)[C@H]2C[C@@H]1CC2)=O.[F:14][C:15]1[CH:33]=[CH:32][C:18]([CH2:19][NH:20][C@H:21]2[C@H:26]3[CH2:27][C@H:23]([CH2:24][CH2:25]3)[C@H:22]2[C:28]([O:30][CH3:31])=[O:29])=[CH:17][CH:16]=1.C([O-])(=O)C.[Na+].FC1C=CC(C=O)=CC=1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C>[F:14][C:15]1[CH:16]=[CH:17][C:18]([CH2:19][NH:20][C@H:21]2[C@H:26]3[CH2:27][C@H:23]([CH2:24][CH2:25]3)[C@H:22]2[C:28]([O:30][CH3:31])=[O:29])=[CH:32][CH:33]=1

Participants

8

Reactant 5

HCID 680234-FluorobenzaldehydeHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 5003444Sodium cyanoborohydrideHCID 86762631HCID 86762631, compound

Product 1

HCID 66674783methyl (1S,2R,3S,4R)-3-[(4-fluorobenzyl)amino]bicyclo[2.2.1]heptane-2-carboxylateYield 98.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

Methyl (1S,2R,3S,4R)-3-[(4-Fluorobenzyl)amino]bicyclo[2.2.1]heptane-2-carboxylate Methyl (1S,2R,3S,4R)-3-aminobicyclo[2.2.1]heptane-2-carboxylate hydrochloride (0.5 g, 2.43 mmol) was dissolved in methanol (12 mL). Sodium acetate (0.4 g, 4.86 mmol) was added followed by 4 Å powdered molecular sieves (0.5 g) and 4-fluoro-benzaldehyde (0.302 g, 2.43 mmol). Sodium cyanoborohydride (0.305 g, 4.86 mmol) was added and the mixture was stirred at 25° C. for 16 h. The mixture was poured into a mixture of aqueous saturated sodium bicarbonate solution (200 mL) and ethyl acetate (300 mL). After shaking, both layers were passed through a plug of Celite. The organic phase was further washed with aqueous saturated sodium bicarbonate solution (100 mL), aqueous saturated brine solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product, methyl (1S,2R,3S,4R)-3-[(4-fluorobenzyl)amino]bicyclo[2.2.1]heptane-2-carboxylate (0.663 g, 2.39 mmol, 98% yield) as a clear oil. LC-MS (ESI) calcd for C16H20FNO2 277.15. found 278.2 [M+H+] (100%).

Workup

  1. stirringAfter shaking
  2. washThe organic phase was further washed with aqueous saturated sodium bicarbonate solution (100 mL), aqueous saturated brine solution (100 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-37b110d50b2e4e95b0eee4c221487702
Source dataset
uspto-grants-2014_08
Patent number
US08815847B2

Reaction notes

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