Sodium cyanoborohydride → 1-[2-(4-bromo-phenyl)-(1R,2R)-cyclopropylmethyl]-(2R)-2-methylpyrrolidine

HRID 73287Notes

Reaction equation

HRID 73287 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[CH:11]=O)=[CH:4][CH:3]=1.C(O)(=O)C(C(C(O)=O)O)O.[CH3:23][C@@H:24]1[CH2:28][CH2:27][CH2:26][NH:25]1.C([BH3-])#N.[Na+]>C(O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[CH2:11][N:25]2[CH2:26][CH2:27][CH2:28][C@H:24]2[CH3:23])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 18651198rel-(1R,2R)-2-(4-Bromophenyl)cyclopropanecarboxaldehydeHCID 23404464(2R)-2-Methylpyrrolidine tartrate

Product 1

HCID 692305391-[2-(4-bromo-phenyl)-(1R,2R)-cyclopropylmethyl]-(2R)-2-methylpyrrolidine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of (1R,2R)-2-(4-bromophenyl)cyclopropanecarbaldehyde (the product of Example 3B, 600 mg, 2.67 mmol) and (R)-2-methylpyrrolidine tartaric acid salt (0.82 g, 3.47 mmol) in ethanol (30 mL) was treated with sodium cyanoborohydride (252 mg 4 mmol). The mixture was stirred at room temperature for two hours. The mixture was quenched with HCl (1N) and then basified to pH=10-12 with NaOH (10%) and partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica gel with 1% to 2% methanol (containing 10% concentrated NH4OH) in dichloromethane to provide the title compound. 1H NMR (300 MHz, CD3OD): 0.89 (m, 1H), 0.98 (m, 1H), 1.14 (d, J=6 Hz, 2H), 1.19 (m, 1H), 1.43 (m, 1H), 1.75 (m, 3H), 1.95 (m, 2H), 2.30 (q, J=9 Hz, 1H), 2.37 (m, 1H), 3.14 (dd, J=12 Hz, J=6 Hz, 1H), 3.22 (m, 1H), 7.00 (d, J=9 Hz, 2H), 7.36 (d, J=9 Hz, 2H). MS (DCl—NH3) m/z 294 (M+H)+.

Workup

  1. customThe mixture was quenched with HCl (1N)
  2. custompartitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified on silica gel with 1% to 2% methanol (containing 10% concentrated NH4OH) in dichloromethane

Sources & evidence

ORD record
ord-d2e5a8d87b4143bdb078cdb02687ab7c
Source dataset
uspto-grants-2014_09
Patent number
US08829041B2

Reaction notes

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