4-bromo-N,N-diethyl-2-[(2R)-2-hydroxypropyl]benzamide → (3R)-6-bromo-3-methyl-3,4-dihydro-1H-isochromen-1-one

HRID 2175778

Reaction equation

HRID 2175778 reaction equation
[Br:1][C:2]1[CH:14]=[CH:13][C:5]([C:6](N(CC)CC)=[O:7])=[C:4]([CH2:15][C@H:16]([OH:18])[CH3:17])[CH:3]=1>Cl.O1CCOCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:13][CH:14]=1)[C:6](=[O:7])[O:18][C@H:16]([CH3:17])[CH2:15]2

Participants

4

Procedure

A solution of 4-bromo-N,N-diethyl-2-[(2R)-2-hydroxypropyl]benzamide (12.2 g, 38.8 mmol) dissolved in 4N HCl in dioxane (200 mL) was stirred at room temperature and monitored by TLC. After 3 days the reaction was partitioned between EtOAc (300 mL) and water (300 mL). The aqueous phase was further extracted with EtOAc (2×250 mL). The combined organic layers were then washed with water (200 mL), brine (200 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was then purified via MPLC (15-30% EtOAc/Hexane) to afford (3R)-6-bromo-3-methyl-3,4-dihydro-1H-isochromen-1-one: 1H NMR (500 MHz; CDCl3): 7.98 (d, J=8.2 Hz, 1H), 7.56 (dd, J=1.5, 8.2 Hz, 1H), 7.45 (s, 1H), 4.71 (m, 1H), 2.94 (m, 2H), 1.55 (d, J=6.3 Hz, 3H); LC-MS: (M+1)+ 241.

Workup

  1. customAfter 3 days the reaction was partitioned between EtOAc (300 mL) and water (300 mL)
  2. extractionThe aqueous phase was further extracted with EtOAc (2×250 mL)
  3. washThe combined organic layers were then washed with water (200 mL), brine (200 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was then purified via MPLC (15-30% EtOAc/Hexane)

Sources & evidence

ORD record
ord-10d94f4369b243c4a4a984d2df7137e7
Source dataset
uspto-grants-2015_06
Patent number
US09062070B2

Linked notes

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