2,3-Dimethylbenzaldehyde → HCID 24904483, compound

HRID 2376066Notes

Reaction equation

HRID 2376066 reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6]C(=O)OC(C)(C)C)[CH2:2]1.[CH3:14][C:15]1[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:16]=1[CH:17]=O.C(N(CC)C(C)C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)C>[CH3:14][C:15]1[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17][N:1]1[CH2:5][CH2:4][C@@H:3]([NH2:6])[CH2:2]1

Participants

6

Reactant 4

HCID 342242,3-DimethylbenzaldehydeHCID 81531DiisopropylethylamineHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 24904483HCID 24904483, compoundYield 17.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1H-NMR (300 MHz, CDCl3) δ 0.77-0.97 (2H, m), 1.05-1.30 (3H, m), 1.36 (3H, t, J=7.1 Hz), 1.40-1.86 (10H, m), 1.97-2.25 (3H, m), 2.37-2.64 (3H, m), 3.84-4.08 (1H, m), 4.30 (2H, q, J=7.1 Hz), 5.59 (1H, br peak), 6.35 (1H, d, J=8.4 Hz), 7.97 (1H, dd, J=8.6, 2.0 Hz), 8.74 (1H, d, J=2.0 Hz). Preparation 372 1) To a mixture of tert-butyl (3R)-3-pyrrolidinylcarbamate (1.00 g), 2,3-dimethylbenzaldehyde (720 mg), N,N-diisopropylethylamine (1.87 mL), and ethanol (10 mL) was added sodium triacetoxyborohydride (2.28 g). After stirring for 3 hours at room temperature, the reaction mixture was partitioned between ethyl acetate and saturated NH4Cl. The organic layer was washed with H2O, dried over MgSO4, filtered, and evaporated in vacuo. 2) To a mixture of above product and ethyl acetate (10 mL) was added 4N hydrogen chloride in ethyl acetate (8.40 mL) at 4° C. After stirring at room temperature for 5 hours, the reaction mixture was neutrized with saturated NaHCO3. The resulting mixture was evaporated in vacuo. The residue was added chloroform, dried over Na2SO4, filtered, and evaporated in vacuo to give (3R)-1-(2,3-dimethylbenzyl)-3-pyrrolidinamine (193 mg). 1H-NMR (300 MHz, CDCl3) δ 1.41-1.53 (1H, m), 2.12-2.46 (3H, m), 2.27 (3H, s), 2.29 (3H, s), 2.64-2.77 (2H, m), 3.42-3.51 (1H, m), 3.58 (2H, s), 7.00-7.14 (3H, m), MS (ES+) m/z 205 (M+1). Preparation 373

Workup

  1. customPreparation 372 1)
  2. customthe reaction mixture was partitioned between ethyl acetate and saturated NH4Cl
  3. washThe organic layer was washed with H2O
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. addition2) To a mixture of above product and ethyl acetate (10 mL)
  8. additionwas added 4N hydrogen chloride in ethyl acetate (8.40 mL) at 4° C
  9. stirringAfter stirring at room temperature for 5 hours
  10. customThe resulting mixture was evaporated in vacuo
  11. additionThe residue was added chloroform
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-440ba02509e24b729c33e7d6e533b45a
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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