Methanol → HCID 18926403, compound

HRID 1744870Notes

Reaction equation

HRID 1744870 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]([OH:33])[CH:14]([N:19]3[CH2:24][CH2:23][C:22]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)([OH:25])[CH2:21][CH2:20]3)[CH2:15][O:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1.CO>[Pd].C(O)(=O)C>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C:22]2([OH:25])[CH2:23][CH2:24][N:19]([CH:14]3[CH:13]([OH:33])[C:12]4[C:17](=[CH:18][C:9]([OH:8])=[CH:10][CH:11]=4)[O:16][CH2:15]3)[CH2:20][CH2:21]2)=[CH:27][CH:28]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 22225732HCID 22225732, compound

Product 1

HCID 18926403HCID 18926403, compoundYield 54.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

A mixture of 3R*4S*7-benzyloxy-3-[4-(4-fluorophenyl)-4-hydroxy-piperidin-1-yl]-chroman-4-ol (0.80 g, 1.78 mmol), 10% palladium on carbon (0.16 g), methanol (40 mL), and acetic acid (0.8 mL) was hydrogenated for 8 hours with a starting pressure of 48.5 psi. The reaction was filtered through celite and the filtrate was concentrated. The residue was stirred vigorously with ether and saturaturated sodium bicarbonate for 1 hour. The solid was washed with water and ether and dried in vacuo. Recrystallization from ethanol yielded 0.35 g (54%) of 3R*4S*3-[4-(4-fluorophenyl)-4-hydroxy-piperidin-1-yl]-chroman-4,7-diol as a white solid which had mp 159-160° C.; NMR DMSO∂σδ7.55-7.47 (m, 2H), 7.11 (t, J=9 Hz, 2H), 7.02 (d, J=8.4 Hz, 1H)k, 6.32 (dd, J=2.3, 8.3 Hz, 1H), 6.15 (d, J=2.3 Hz 1H), 5.10-4.50 (br m with s at 4.63, 3H), 4.23 (dd, J=2.8, 10.3 Hz, 1H), 4.04 (t, J=10.5 Hz, 1H), 2.99 (br d, J=10.8 Hz, 1H), 2.86 (br d, J=10.7 Hz, 1H), 2.73-2.50 (m, 3H), 2.08-1.90 (m, 2H), 1.58 (br d, J=13 Hz, 2H).

Workup

  1. filtrationThe reaction was filtered through celite
  2. concentrationthe filtrate was concentrated
  3. customfor 1 hour
  4. washThe solid was washed with water and ether
  5. customdried in vacuo
  6. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-2b3a96c6da1e42f6ad6c8366e17058ab
Source dataset
uspto-grants-2006_03
Patent number
US07019016B2

Reaction notes

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