Lithium Hydroxide → HCID 59902362, compound

HRID 2230145Notes

Reaction equation

HRID 2230145 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-]>C(Cl)Cl.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

7

Reactant 4

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

Product 1

HCID 59902362HCID 59902362, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

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 CH2Cl2 (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. CH2Cl2 was added and the mixture was washed once with water, twice with iN 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 concentrated in vacuo. The residue 6% NaHCO1, 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. washthe mixture was washed once with water, twice with iN HCl, once with water, twice with 6% NaHCO3
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in THF (1 mL)
  7. temperaturecooled to 0° C
  8. waitto proceed at 0° C. for 4 hours
  9. customThe reaction mixture was quenched with saturated NH4Cl
  10. customthe THF was removed
  11. concentrationby concentrated in vacuo
  12. dry with materialThe residue 6% NaHCO1, dried over Na2SO4
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-56d61f3ec8734e219412bdf48a1df661
Source dataset
uspto-grants-2002_07
Patent number
US06423710B1

Reaction notes

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