Lithium Hydroxide → HCID 59902362, compound

HRID 2084529Notes

Reaction equation

HRID 2084529 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 1N HCl, once with water, twice with 6% NaHCO2, 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 CH2Cl2, 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. washthe mixture was washed once with water, twice with 1N HCl, once with water, twice with 6% NaHCO2
  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 by concentration in vacuo
  11. washwashed twice with 6% NaHCO3
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fc1080beb2ed428098c5a92225f17ea6
Source dataset
uspto-grants-2004_04
Patent number
US06716871B2

Reaction notes

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