Borane;tetrahydrofuran → HCID 57429430, compound

HRID 1640020Notes

Reaction equation

HRID 1640020 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][N:8]([C:13]3[CH:18]=[CH:17][C:16]([CH:19]([CH3:23])[C:20](O)=[O:21])=[CH:15][CH:14]=3)[C:9]2=[O:12])=[CH:5][CH:4]=1.B.O1CCCC1>O1CCCC1.O.C(OCC)(=O)C>[OH:21][CH2:20][CH:19]([C:16]1[CH:15]=[CH:14][C:13]([N:8]2[CH2:7][C:6]3[C:10](=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:9]2=[O:12])=[CH:18][CH:17]=1)[CH3:23]

Participants

6

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 57429431HCID 57429431, compound

Product 1

HCID 57429430HCID 57429430, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-(4-(6-methoxy-1-oxoisoindolin-2-yl)phenyl)propanoic acid (0.102 g, 0.33 mmol) and borane-tetrahydrofuran complex (0.83 mL, 1 M in tetrahydrofuran, 0.83 mmol) in tetrahydrofuran (2 mL) at 0° C. was stirred for 3 h. After this time, the reaction mixture was diluted with water (5 mL) and ethyl acetate (5 mL) and the mixture stirred vigorously for 18 h at room temperature. The aqueous layer was separated and extracted with ethyl acetate (25 mL), and the combined organic layers dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford an off-white solid. Purification by flash chromatography (silica, 1:1 ethyl acetate/hexanes) afforded 2-(4-(1-hydroxypropan-2-yl)phenyl)-6-methoxyisoindolin-1-one (0.081 g, 84%) as a white solid: mp 135-138° C.; 1H NMR (300 MHz, CDCl3) δ 7.81 (dd, J=8.6, 19 Hz, 2H), 7.41-7.39 (m, 2H), 7.31 (d, J=8.6 Hz, 2H), 7.16 (dd, J=8.4, 2.4 Hz, 1H), 4.79 (s, 2H), 3.89 (s, 3H), 3.72 (d, J=6.8 Hz, 2H), 2.98 (q, J=6.9 Hz, 1H), 1.30 (d, J=7.0 Hz, 3H); ESI MS m/z 298 [M+H]+.

Workup

  1. stirringthe mixture stirred vigorously for 18 h at room temperature
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (25 mL)
  4. dry with materialthe combined organic layers dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford an off-white solid
  8. customPurification by flash chromatography (silica, 1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4f1ab116eba74d77a2d85e73cc3ec819
Source dataset
uspto-grants-2012_02
Patent number
US08110681B2

Reaction notes

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