Water → 2-[4-((R)-1-Methyl-pyrrolidin-2-ylmethoxy)-phenyl]-2,3-dihydro-1H-isoindole

HRID 2242882Notes

Reaction equation

HRID 2242882 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].C(O[C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@@H:15]1[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]2[C:35](=O)[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:28]2=O)=[CH:23][CH:22]=1)=O)(C)(C)C.O.[OH-].[Na+]>C1COCC1>[CH3:12][N:14]1[CH2:18][CH2:17][CH2:16][C@@H:15]1[CH2:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([N:27]2[CH2:28][C:29]3[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:35]2)=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 58900146(R)-2-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 589001312-[4-((R)-1-Methyl-pyrrolidin-2-ylmethoxy)-phenyl]-2,3-dihydro-1H-isoindoleYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 25 mL press resistant vial which contained a suspension of LiAlH4 (100 mg, 3 mmol) in anhydrous THF (15 mL) was added the product from step 1 (120 mg, 0.3 mmol) at −78° C. The reaction mixture was allowed to warm to rt and stir at rt for 2 h then was heated to 78° C. and stirred at 78° C. for 24 h. After cooled to 5° C., 1 eq of water was added to the mixture which was followed by addition of 1 eq of 15% NaOH and then 3 eq of water. The solid which formed was filtered out and washed with THF water (2×20 mL). The combined organic solvent was removed under vacuo to obtain the crude product which was purified by recrystallization with ether-EtOAc-hexane to afford the title product, (50 mg, 57%);LCMS; 99%, ESI+ Calcd: 308.4 m/z, found: 309.7 m/z (M+1);

Workup

  1. temperaturethen was heated to 78° C.
  2. stirringstirred at 78° C. for 24 h
  3. temperatureAfter cooled to 5° C.
  4. customThe solid which formed
  5. filtrationwas filtered out
  6. washwashed with THF water (2×20 mL)
  7. customThe combined organic solvent was removed under vacuo
  8. customto obtain the crude product which
  9. customwas purified by recrystallization with ether-EtOAc-hexane

Sources & evidence

ORD record
ord-7b25ea47e7c241b9bb1b24461c76ebc9
Source dataset
uspto-grants-2010_03
Patent number
US07674802B2

Reaction notes

Loading…