Lithium borohydride → 2-methyl-2,3-dihydro-1H-isoindol-5-amine

HRID 472442Notes

Reaction equation

HRID 472442 reaction equation
[BH4-].[Li+].C(O[C:8]([N:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([NH2:19])[CH:16]=2)[CH2:11]1)=O)(C)(C)C>O1CCCC1>[CH3:8][N:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([NH2:19])[CH:16]=2)[CH2:11]1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 22591361tert-butyl 5-amino-2,3-dihydro-1H-isoindole-2-carboxylate

Product 1

HCID 219881602-methyl-2,3-dihydro-1H-isoindol-5-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

166 e) To a cooled solution of 2.0 M of lithium tetrahydroborate in tetrahydrofuran (13 mL, 26 mmol) at 5° C. was added dropwise a solution of 5-amino-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (1.0 g, 4.3 mmol) in tetrahydrofuran (50 mL). Gas evolution was noted. The mixture was stirred for 1 hour at 5° C. then warmed to room temperature and stirred for 24 hours. The mixture was cooled to 5° C. in a ice/water bath and the reaction was quenched by addition of sodium sulfate decahydrate (3 g). Gas evolution noted. The mixture was stirred for 2 hours at room temperature. The suspension was filtered through a plug of diatomaceous earth and rinsed with tetrahydrofuran. The filtrate was dried over magnesium sulfate, filtered and evaporated. The residue was purified via flash chromatography (silica gel column and 0%→20% methanol: dichloromethane). 2-Methyl-2,3-dihydro-1H-isoindol-5-ylamine was isolated as an orange solid (0.271 g, 43%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 6.82 (d, J=7.9 Hz, 1H), 6.41 (s, 1H), 6.37 (d, J=8.1 Hz, 1H), 4.86 (br s, 2H), 3.64 (s, 2H), 3.62 (s, 2H), 2.42 (s, 3H). MS=149 (MH)+.

Workup

  1. temperaturethen warmed to room temperature
  2. stirringstirred for 24 hours
  3. temperatureThe mixture was cooled to 5° C. in a ice/water bath
  4. customthe reaction was quenched by addition of sodium sulfate decahydrate (3 g)
  5. stirringThe mixture was stirred for 2 hours at room temperature
  6. filtrationThe suspension was filtered through a plug of diatomaceous earth
  7. washrinsed with tetrahydrofuran
  8. dry with materialThe filtrate was dried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified via flash chromatography (silica gel column and 0%→20% methanol: dichloromethane)

Sources & evidence

ORD record
ord-d7b8270eba464df0810bd07003e263b0
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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