Sodium Bicarbonate → methyl (1R,2S,3R,4S)-3-[(4-fluoro-3-methylbenzyl)amino]-7-oxabicyclo[2.2.1]heptane-2-carboxylate

HRID 1617038Notes

Reaction equation

HRID 1617038 reaction equation
[NH2:1][C@H:2]1[C@H:7]2[O:8][C@H:4]([CH2:5][CH2:6]2)[C@H:3]1[C:9]([O:11][CH3:12])=[O:10].[F:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][C:15]=1[CH3:22].C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C.C(O)(=O)C>[F:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][NH:1][C@H:2]2[C@H:7]3[O:8][C@H:4]([CH2:5][CH2:6]3)[C@H:3]2[C:9]([O:11][CH3:12])=[O:10])=[CH:16][C:15]=1[CH3:22]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 27348744-Fluoro-3-methylbenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 39345633methyl (1R,2S,3R,4S)-3-amino-7-oxabicyclo[2.2.1]heptane-2-carboxylate

Product 1

HCID 66673816methyl (1R,2S,3R,4S)-3-[(4-fluoro-3-methylbenzyl)amino]-7-oxabicyclo[2.2.1]heptane-2-carboxylateYield 88.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of methyl (1R,2S,3R,4S)-3-amino-7-oxabicyclo[2.2.1]heptane-2-carboxylate (400 mg, 2.34 mmol) in methanol (8 mL) under a nitrogen atmosphere, 4-fluoro-3-methyl-benzaldehyde (0.29 mL, 2.34 mmol) was added. The mixture was stirred for 10 min, and then acetic acid (0.4 mL) was added followed by sodium cyanoborohydride (368 mg, 5.85 mmol). The resulting mixture was stirred at 25° C. for 16 h, and then poured into a mixture of saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous brine solution, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo to afford the desired product, methyl (1R,2S,3R,4S)-3-[(4-fluoro-3-methylbenzyl)amino]-7-oxabicyclo[2.2.1]heptane-2-carboxylate (610 mg, 2.08 mmol, 80%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 1.40 (2H, m), 1.76 (2H, m), 2.27 (3H, d, J=2.0 Hz), 2.86 (1H, d, J=7.6 Hz), 3.16 (1H, d, J=8.4 Hz), 3.64 (1H, d, J=13.2 Hz), 3.74 (3H, s), 3.79 (1H, d, J=13.6 Hz), 4.46 (1H, d, J=5.2 Hz), 4.73 (1H, d, J=4.8 Hz), 6.92 (2H, m), 7.07 (2H, m).

Workup

  1. stirringThe resulting mixture was stirred at 25° C. for 16 h
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layers were washed with saturated aqueous brine solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-cf1b546274dd447494b14880aae8d201
Source dataset
uspto-grants-2014_07
Patent number
US08765741B2

Reaction notes

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