Methanol → HCID 18926403, compound

HRID 968276Notes

Reaction equation

HRID 968276 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 saturated 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∂σ δ7.55-7.47 (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. washThe solid was washed with water and ether
  4. customdried in vacuo
  5. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-053c0f202f95442cabac2051f8efa072
Source dataset
uspto-grants-2005_10
Patent number
US06958351B2

Reaction notes

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