Sodium Hydroxide → 1-{[(1S,2S)-2-(4-bromophenyl)cyclopropyl]methyl}-(2S)-2-methylpyrrolidine

HRID 515030Notes

Reaction equation

HRID 515030 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+].[OH-].[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

6

Reactant 4

HCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 57515374trans-2-(4-Bromophenyl)cyclopropane-1-carbaldehydeHCID 66601405(S)-2-methylpyrrolidine tartrate

Product 1

HCID 575153751-{[(1S,2S)-2-(4-bromophenyl)cyclopropyl]methyl}-(2S)-2-methylpyrrolidine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of (1S,2S)-2-(4-bromophenyl)cyclopropanecarbaldehyde (the product of Example 1C, 820 mg, 3.64 mmol) and (S)-2-methylpyrrolidine tartaric acid salt (1.12 g, 4.73 mmol) in ethanol (30 mL) was treated with sodium cyanoborohydride (345 mg 5.46 mmol). The mixture was stirred at room temperature for two hours. The mixture was basified to pH=10-12 with NaOH (10%) and partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica gel eluting with 1% to 2% methanol (containing 10% concentrated NH4OH) in dichloromethane to provide the title compound. 1H NMR (300 MHz, CDCl3): δ 0.87-0.92(m, 1H), 0.97-1.02 (m, 1H), 1.16 (d, J=6 Hz, 2H), 1.22 (m, 1H), 1.39-1.49 (m, 1H), 1.73-1.81 (m, 3H), 2.0 (m, 2H), 2.36 (q, J=6 Hz, 1H), 2.45 (m, 1H), 3.13 (dd, J=12 Hz, J=6 Hz, 1H), 3.25 (m, 1H), 7.00 (d, J=6 Hz, 2H), 7.37 (d, J=6 Hz, 2H). MS (DCl—NH3) m/z 294 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-32dd72cd11384a94b11f85c591b3c3e3
Source dataset
uspto-grants-2015_08
Patent number
US09108948B2

Reaction notes

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