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

HRID 272925Notes

Reaction equation

HRID 272925 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 (Note: very exothermic). 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 (Note: very exothermic, gas evolution, temperature maintained below 16° C., toward the end of the quench the reaction mixture sets and then becomes freer with continued stirring.). 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 slats were removed by filtration and rinsed with tetrahydrofuran (3×150 ml). The combined filtrates were evaporated to dryness at 40° C. to yield title compound (12.1 g, 94%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.25 (d, 2H), 6.90 (d, 2H), 4.05 (t, 2H), 3.80 (dt, 2H), 3.55 (td, 2H), 2.60 (t, 2H), 2.62-2.41 (m, 4H), 2.10 (dt, 2H), 2.00 (p, 2H), 2.00-1.85 (m, 2H), 1.95-1.72 (m, 4H).

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. temperaturevery exothermic, gas evolution, temperature maintained below 16° C., toward the end of the
  9. customquench the reaction mixture sets
  10. 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)
  11. stirringthe resulting white suspension stirred vigorously for 30 minutes at 18-25° C
  12. customThe slats were removed by filtration
  13. washrinsed with tetrahydrofuran (3×150 ml)
  14. customThe combined filtrates were evaporated to dryness at 40° C.

Sources & evidence

ORD record
ord-5a77d302de104b699baa19e591d3d239
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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