Benzaldehyde → (1S,2R,3S,4R)-3-benzylamino-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

HRID 424256Notes

Reaction equation

HRID 424256 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([O:11][C:12]([C@H:14]1[C@@H:19]([NH2:20])[C@H:18]2[CH2:21][C@@H:15]1[CH2:16][CH2:17]2)=[O:13])[CH3:10].C([BH3-])#N.[Na+]>C(O)(=O)C.CO>[CH2:9]([O:11][C:12]([C@H:14]1[C@@H:19]([NH:20][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C@H:18]2[CH2:21][C@@H:15]1[CH2:16][CH2:17]2)=[O:13])[CH3:10]

Participants

6

Reactant 3

HCID 240BenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 13396165diexo-3-Amino-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

Product 1

HCID 66673783(1S,2R,3S,4R)-3-benzylamino-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl esterYield 72%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

Benzaldehyde (0.454 mL, 4.47 mmol) and 10 drops glacial acetic acid were added sequentially to a solution of (1S,2R,3S,4R)-3-amino-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester (prepared as described in Example 6k, 0.82 g, 4.47 mmol) in methanol (15 mL) at 25° C. Sodium cyanoborohydride (0.703 g, 11.2 mmol) was added, and the reaction mixture was stirred at 25° C. for 2 h, and then was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (Teledyne Isco RediSep column; 0 to 35% ethyl acetate in hexanes) to afford the desired product, (1S,2R,3S,4R)-3-benzylamino-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester (0.875 g, 3.22 mmol, 72%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 1.06-1.16 (2H, m), 1.20-1.23 (2H, m), 1.28 (3H, t, J=7.0 Hz), 1.46-1.61 (2H, m), 1.93-1.97 (1H, m), 2.33-2.34 (1H, m), 2.43-2.44 (1H, m), 2.59-2.62 (1H, m), 2.98-3.00 (1H, m), 3.71 (1H, d, J=14.0 Hz), 3.85 (1H, d, J=13.3 Hz), 4.14 (2H, q, J=7.3 Hz), 7.20-7.24 (1H, m), 7.27-7.33 (4H, m).

Workup

  1. customwas partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL)
  2. dry with materialThe organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography (Teledyne Isco RediSep column; 0 to 35% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bcaafdd1316940149533572753e837f6
Source dataset
uspto-grants-2012_01
Patent number
US08101800B2

Reaction notes

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