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

HRID 515035Notes

Reaction equation

HRID 515035 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): δ 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-c39ced6172d84ae9936117f69dbb7883
Source dataset
uspto-grants-2015_08
Patent number
US09108948B2

Reaction notes

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