Nitrogen → (3R)-1-[(1R,2R)-2-[2-(3-hydroxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinol

HRID 1799783Notes

Reaction equation

HRID 1799783 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([CH2:17][CH2:18][O:19][C@@H:20]2[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]2[N:26]2[CH2:30][CH2:29][C@@H:28]([OH:31])[CH2:27]2)[CH:12]=[CH:13][C:14]=1[O:15][CH3:16])C1C=CC=CC=1.N#N.[H][H]>[Pd].CO>[OH:8][C:9]1[CH:10]=[C:11]([CH2:17][CH2:18][O:19][C@@H:20]2[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]2[N:26]2[CH2:30][CH2:29][C@@H:28]([OH:31])[CH2:27]2)[CH:12]=[CH:13][C:14]=1[O:15][CH3:16]

Participants

6

Reactant 3

HCID 947NitrogenHCID 66686409(3R)-1-[(1R,2R)-2-[2-(3-benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinolHCID 178418361HCID 178418361, compound

Product 1

HCID 16042424(3R)-1-[(1R,2R)-2-[2-(3-hydroxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinol

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To compound (3R)-1-[(1R,2R)-2-[2-(3-benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinol (35.0 g, 75.8 mmol) was added methanol (150 mL). This solution was transferred to a Parr bottle and Pd/C (10% wt/wt on activated carbon) was added portion-wise while maintaining a N2 atmosphere through the reaction mixture. Hydrogen pressure (60 psi) was then applied and the vessel shaken for 3 hours, after which HPLC showed complete consumption of the starting material. The reaction mixture was filtered through a pad of Celite and the filtrate was concentrated to give (3R)-1-[(1R,2R)-2-[2-(3-hydroxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinol as a colorless syrup. The crude product was dissolved in 1 M aqueous HCl solution (450 mL) and washed with chloroform (8×250 mL). The aqueous layer was then saturated with solid NaCl (100 g) and the solution was extracted with dichloromethane (8×200 mL). The combined dichloromethane extracts were dried (anhydrous MgSO4), filtered, and concentrated under reduced pressure to give 3R)-1-[(1R,2R)-2-[2-(3-hydroxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinol as a colorless syrup; 1H NMR (400 MHz, D2O) δ 7.01 (d, H, J=8.0), 6.86-6.83 (m, 2H), 4.42-4.36 (m, 1H), 4.02 (overlapping dt, 1H, J=5.2, J=10.1), 3.85 (s, 3H), 3.67-3.55 (m, 1H), 3.46-2.81 (m, 7H), 2.77-2.70 (m, 1H), 2.34-2.27 (m, 1H), 2.11-1.74 (m, 5H), 1.41-1.10 (m, 4H); IR: 3439 (O—H stretch), 1592, 1510, 1098, 1022 cm−1; MS (ESI) 336.1 (M+1)+.

Workup

  1. additionwas added portion-wise
  2. customconsumption of the starting material
  3. filtrationThe reaction mixture was filtered through a pad of Celite
  4. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-d3e1e95fde8b499595a7c13583dcab18
Source dataset
uspto-grants-2013_01
Patent number
US08344162B2

Reaction notes

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