Water → (1S,2S)-1-(4-benzyloxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol

HRID 413950Notes

Reaction equation

HRID 413950 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:31])[C@@H:16]([N:18]2[CH2:23][CH2:22][C:21]([OH:30])([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:20][CH2:19]2)[CH3:17])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Li+].O>C(O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]([OH:31])[C@@H:16]([N:18]2[CH2:19][CH2:20][C:21]([OH:30])([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:22][CH2:23]2)[CH3:17])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 4148881Lithium borohydrideHCID 10201949(2S)-1-(4-Benzyloxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanone

Product 1

HCID 10127000(1S,2S)-1-(4-benzyloxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanolYield 86.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
22.5 °C

Procedure

Over 20 minutes, (2S)-1-(4-benzyloxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanone (75 g, 0.18 mol) was added to a suspension of lithium borohydride (3.15 g, 0.15 mol) in ethanol (0.75 L) maintained under a nitrogen atmosphere at 20 to 25° C. After stirring for about 5 minutes, a mild exotherm occurred raising the temperature to 27° C. The slurry was stirred for 42 hours at 20 to 25° C. when HPLC indicated that the reaction was complete. Water (37.5 mL) was added and the slurry was granulated for 1 hour at 20 to 25° C. The white solid was filtered and then washed with ethanol (75 mL), water (150 mL), and finally ethanol (75 mL). The product was dried in vacuo at 40 to 45° C. for 20 hours to give 65.3 g of the title compound. The (1S,2S) amino alcohol product was obtained in 78.3% yield and contained only 2.3% of diastereomers. M.p. 158-161° C., [α]D25+38.7 (c 6.1, CH3OH)

Workup

  1. temperaturea mild exotherm occurred raising the temperature to 27° C
  2. stirringThe slurry was stirred for 42 hours at 20 to 25° C. when HPLC
  3. waitthe slurry was granulated for 1 hour at 20 to 25° C
  4. filtrationThe white solid was filtered
  5. washwashed with ethanol (75 mL), water (150 mL), and finally ethanol (75 mL)
  6. customThe product was dried in vacuo at 40 to 45° C. for 20 hours

Sources & evidence

ORD record
ord-520a3cf1120b4e98b476ee777e9da7e6
Source dataset
uspto-grants-2003_05
Patent number
US06570018B2

Reaction notes

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