Reserpine → Methyl (3beta,16beta,17alpha,18beta,20alpha)-18-hydroxy-11,17-dimethoxyyohimban-16-carboxylate

HRID 450009Notes

Reaction equation

HRID 450009 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:11]3[CH2:12][CH2:13][N:14]4[CH2:19][C@H:18]5[CH2:20][C@@H:21]([O:30]C(C6C=C(OC)C(OC)=C(OC)C=6)=O)[C@H:22]([O:28][CH3:29])[C@@H:23]([C:24]([O:26][CH3:27])=[O:25])[C@H:17]5[CH2:16][C@@H:15]4[C:10]=3[NH:9][C:7]=2[CH:8]=1.C[O-].[Na+]>CO>[CH3:29][O:28][C@@H:22]1[C@@H:23]([C:24]([O:26][CH3:27])=[O:25])[C@@H:17]2[C@@H:18]([CH2:19][N:14]3[C@H:15]([CH2:16]2)[C:10]2[NH:9][C:7]4[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=4[C:11]=2[CH2:12][CH2:13]3)[CH2:20][C@H:21]1[OH:30]

Participants

4

Reactant 2

HCID 5770ReserpineHCID 10942334Sodium Methoxide2×

Product 1

HCID 73532Methyl (3beta,16beta,17alpha,18beta,20alpha)-18-hydroxy-11,17-dimethoxyyohimban-16-carboxylateYield 97.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of reserpine (1.00 g, 1.64 mmol), NaOMe (0.20 g, 3.61 mmol), and MeOH (50 mL) was refluxed for 4 h (more NaOMe was added twice), cooled, and concentrated to one-third the volume. The solution was diluted with water (60 mL) and acidified to pH=1 with concentrated HCl. The water layer was washed with Et2O repeatedly and made basic with concentrated NH4OH and repeatedly extracted with CH2Cl2 (4×30 mL). The combined organic phases were dried, filtered, and concentrated to give a colorless solid (0.66 g, 97%). 1H NMR (CDCl3) δ 7.85 (s, 1H), 7.32 (d, J=8.4 Hz, 1H), 6.82-6.74 (m, 2H), 4.41 (s, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 3.73-3.68 (m, 1H), 3.59 (s, 3H), 3.58-3.45 (m, 3H), 3.18-3.15 (m, 2H), 3.01-2.91 (m, 2H), 2.68-2.43 (m, 4H), 2.26-2.18 (m, 2H), 1.98-1.75 (m, 4H), 1.27-1.18 (m, 2H); 13C NMR (CDCl3) δ 173.5, 156.2, 136.5, 130.9, 122.3, 118.6, 108.99, 108.03, 95.3, 81.6, 75.3, 66.0, 61.1, 58.4, 55.9, 53.8, 51.9, 51.5, 51.3, 49.4, 34.6, 32.9, 32.5, 24.4, 18.5, 16.9, 15.4.

Workup

  1. additionwas added twice),
  2. temperaturecooled
  3. concentrationconcentrated to one-third the volume
  4. additionThe solution was diluted with water (60 mL)
  5. washThe water layer was washed with Et2O repeatedly
  6. extractionrepeatedly extracted with CH2Cl2 (4×30 mL)
  7. customThe combined organic phases were dried
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-bf9b64a63a58430cada0f3cd4ab06deb
Source dataset
uspto-grants-2013_07
Patent number
US08486957B2

Reaction notes

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