Water → HCID 22225732, compound

HRID 1744869Notes

Reaction equation

HRID 1744869 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[C:14]([N:20]3[CH2:25][CH2:24][C:23]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)([OH:26])[CH2:22][CH2:21]3)[C:15](=O)[O:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].[OH2:36]>C(O)C.O1CCCC1>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]([OH:36])[CH:14]([N:20]3[CH2:25][CH2:24][C:23]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)([OH:26])[CH2:22][CH2:21]3)[CH2:15][O:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydride2×HCID 22225755HCID 22225755, compound

Product 1

HCID 22225732HCID 22225732, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a slurry of 7-benzyloxy-3-[4-(4-fluorophenyl)-4-hydroxy-piperidine-1-yl]-chromenone (8.24 g, 18.5 mmol) in ethanol (400 mL) and tetrahydrofuran (600 mL) was added sodium borohydride (7.0 g, 185 mmol). The mixture was stirred overnight. Additional sodium borohydride (7.0 g) was added and the reaction mixture was stirred for 3 days. Water was added and the solvent was removed at reduced pressure at 45° C. The solids which formed were collected and washed well with water and then ether. The solid was further dried in vacuo overnight to give 5.01 g, 60% of 3R*4S*7-benzyloxy-3-[4-(4-fluorophenyl)-4-hydroxy-piperidin-1-yl]-chroman-4-ol which was suitable for use without further purification. A sample recrystallized from ethyl acetate/chloroform had mp. 194-195° C.; NMR δ7.56-7.30 (m, 8H), 7.06 (long range coupled t, J=8.7 Hz, 2H) 6.63 (dd, J=2.4, 8.5 Hz, 1H), 6.47 (d, J=2.4 Hz, 1H), 5.04 (s, 2H), 4.77 (d, J=4.5Hz, 1H), 4.37 (dd, J=3.5, 10.4Hz, 1H), 4.13 (t, J=10.4 Hz, 1H), 3.82 (brs, 1H), 3.11 (br d, J=11.2 Hz, 1H), 2.92-2.71 (m, 4H), 2.21-2.06 (m, 2H), 1.87-1.73 (m, 2H), 1.54 (s,1H).

Workup

  1. stirringthe reaction mixture was stirred for 3 days
  2. customthe solvent was removed at reduced pressure at 45° C
  3. customThe solids which formed
  4. customwere collected
  5. washwashed well with water
  6. customThe solid was further dried in vacuo overnight

Sources & evidence

ORD record
ord-488b97ed0d8245dc9bb2784f5fe8bf4a
Source dataset
uspto-grants-2006_03
Patent number
US07019016B2

Reaction notes

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