Lithium Hydroxide → HCID 59902362, compound

HRID 890685Notes

Reaction equation

HRID 890685 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([C@@H:14]3[CH2:18][NH:17][CH2:16][C@:15]3([CH2:20][OH:21])[CH3:19])[CH:9]=[CH:10][C:11]=2[O:12][CH3:13])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[CH2:31]([O:38][CH2:39][C:40](Cl)=[O:41])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[Li+].[OH-]>O>[CH2:31]([O:38][CH2:39][C:40]([N:17]1[CH2:18][C@@H:14]([C:8]2[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:6]([O:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)[CH:7]=2)[C@@:15]([CH2:20][OH:21])([CH3:19])[CH2:16]1)=[O:41])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 177085Benzyloxyacetyl chlorideHCID 10286228HCID 10286228, compound

Product 1

HCID 59902362HCID 59902362, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

[4-(S)-(3-Cyclopropylmethoxy-4-methoxyphenyl)-3-(S)-methylpyrrolidin-3-yl]methanol (100 mg, 0.34 mmol) was dissolved in CH2C2 (1.7 mL), and the solution was cooled to 0° C. DIEA (144 μL, 0.82 mmol) was added, followed by benzyloxyacetyl chloride (114 μL, 0.72 mmol). The reaction was allowed to warm to room temperature slowly and stirred for 18 hours. Water was added (0.25 mL) and the reaction was stirred for 1.5 hours. CH2C2 was added and the mixture was washed once with water, twice with 1N HCl, once with water, twice with 6% NaHCO3, then dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in THF (1 mL) and cooled to 0° C. A solution of LiOH in water (1.36M, 1 mL, 1.36 mmol) was added and the hydrolysis was allowed to proceed at 0° C. for 4 hours. The reaction mixture was quenched with saturated NH4Cl, and the THF was removed by concentration in vacuo. The residue was resuspended in CH2C2, and washed twice with 6%. NaHCO3, dried over Na2SO4 and concentrated in vacuo.

Workup

  1. temperatureto warm to room temperature slowly
  2. stirringthe reaction was stirred for 1.5 hours
  3. additionCH2C2 was added
  4. washthe mixture was washed once with water, twice with 1N HCl, once with water, twice with 6% NaHCO3
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in THF (1 mL)
  8. temperaturecooled to 0° C
  9. waitto proceed at 0° C. for 4 hours
  10. customThe reaction mixture was quenched with saturated NH4Cl
  11. customthe THF was removed by concentration in vacuo
  12. washwashed twice with 6%
  13. dry with materialNaHCO3, dried over Na2SO4
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9aaf09285f964738b4b814ef0864a568
Source dataset
uspto-grants-2006_02
Patent number
US06998416B2

Reaction notes

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