Sodium Bicarbonate → methyl (1S,2R,3S,4R)-3-(4-fluoro-3-methyl-benzylamino)-bicyclo[2.2.1]heptane-2-carboxylate

HRID 548317Notes

Reaction equation

HRID 548317 reaction equation
Cl.[NH2:2][C@H:3]1[C@H:8]2[CH2:9][C@H:5]([CH2:6][CH2:7]2)[C@H:4]1[C:10]([O:12][CH3:13])=[O:11].C([O-])(=O)C.[Na+].[F:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][C:21]=1[CH3:28].C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C>[F:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][NH:2][C@H:3]2[C@H:8]3[CH2:9][C@H:5]([CH2:6][CH2:7]3)[C@H:4]2[C:10]([O:12][CH3:13])=[O:11])=[CH:22][C:21]=1[CH3:28]

Participants

8

Reactant 5

HCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 27348744-Fluoro-3-methylbenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 66674231Methyl (1S,2R,3S,4R)-3-aminobicyclo[2.2.1]heptane-2-carboxylate Hydrochloride

Product 1

HCID 66674907methyl (1S,2R,3S,4R)-3-(4-fluoro-3-methyl-benzylamino)-bicyclo[2.2.1]heptane-2-carboxylateYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

Methyl (1S,2R,3S,4R)-3-aminobicyclo[2.2.1]heptane-2-carboxylate hydrochloride (prepared as described in Example 6c, 0.32 g, 1.56 mmol) was dissolved in methanol (8 mL). Sodium acetate (0.26 g, 3.12 mmol) was added followed by 4 Å powdered molecular sieves (0.32 g) and 4-fluoro-3-methyl benzaldehyde (0.19 mL, 1.56 mmol). Sodium cyanoborohydride (0.24 g, 3.12 mmol) was added and the mixture was stirred at 25° C. for 16 h. The mixture was poured into a mixture of saturated aqueous sodium bicarbonate solution (20 mL) and ethyl acetate (30 mL). After shaking, both layers were passed through a plug of Celite. The organic layer was further washed with saturated aqueous sodium bicarbonate solution (10 mL), saturated aqueous brine solution (10 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product, methyl (1S,2R,3S,4R)-3-(4-fluoro-3-methyl-benzylamino)-bicyclo[2.2.1]heptane-2-carboxylate (0.35 g, 1.20 mmol, 77%), as a clear oil. LC-MS (ESI) calcd for C17H22FNO2 291.36, found 292.5 [M+H+].

Workup

  1. stirringAfter shaking
  2. washThe organic layer was further washed with saturated aqueous sodium bicarbonate solution (10 mL), saturated aqueous brine solution (10 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-395f5b0641134b7d984fa804fd2510de
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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