Water → {4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methanol

HRID 272863Notes

Reaction equation

HRID 272863 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[N:7]1([CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3([C:28](OC)=[O:29])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1.O>O1CCCC1>[N:7]1([CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3([CH2:28][OH:29])[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)=[CH:18][CH:17]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

5

Reactant 3

HCID 962WaterHCID 21226445Aluminium lithium hydrideHCID 68575572methyl 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carboxylate

Product 1

HCID 59837459{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methanolYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
2.5 °C

Procedure

Anhydrous tetrahydrofuran (141 ml, 10 vol) was charged rapidly onto stirred and cooled (0-5° C.) lithium aluminium hydride (6.2 g, 0.1634 mol, 0.44 wt) under nitrogen. The resulting slurry was cooled to 0-5° C. and then a solution of methyl 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carboxylate (14.1 g, 0.04058 mol) in tetrahydrofuran (99 ml, 7 vol) was added dropwise over 30 minutes maintaining 0-5° C. On complete addition the reaction was allowed to warm to room temperature over 30 minutes and stirred at 18-25° C. for 30 minutes, LC analysis showed the reaction to be complete. The mixture was cooled to 0 to 5° C., a 1:1 mixture of tetrahydrofuran and water (18.6 ml, 1.32 vol) was added very slowly. The mixture was further quenched with 20% w/v sodium hydroxide solution (6.2 ml, 0.44 vol) and water (18.6 ml, 1.32 vol) and the resulting white suspension stirred vigorously for 30 minutes at 18-25° C. The salts were removed by filtration and rinsed with tetrahydrofuran (3×150 ml). The combined filtrates were evaporated to dryness at 40° C. to yield {4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}methanol (12.1 g, 94%) as a white solid.

Workup

  1. temperaturemaintaining 0-5° C
  2. additionOn complete addition the reaction
  3. temperatureto warm to room temperature over 30 minutes
  4. stirringstirred at 18-25° C. for 30 minutes
  5. customthe reaction
  6. temperatureThe mixture was cooled to 0 to 5° C.
  7. additionwas added very slowly
  8. customThe mixture was further quenched with 20% w/v sodium hydroxide solution (6.2 ml, 0.44 vol) and water (18.6 ml, 1.32 vol)
  9. stirringthe resulting white suspension stirred vigorously for 30 minutes at 18-25° C
  10. customThe salts were removed by filtration
  11. washrinsed with tetrahydrofuran (3×150 ml)
  12. customThe combined filtrates were evaporated to dryness at 40° C.

Sources & evidence

ORD record
ord-017085cd2f0340d8b02b0790b47b6623
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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