Water → (R)-1-(2-methoxy-4-nitrophenoxy)propan-2-ol

HRID 1916362Notes

Reaction equation

HRID 1916362 reaction equation
CCOCC.[CH3:6][O:7][C:8]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:9]=1[O:10][CH2:11][C@H:12]1[CH2:14][O:13]1.CNC.B.O>C(Cl)Cl>[CH3:6][O:7][C:8]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:9]=1[O:10][CH2:11][C@H:12]([OH:13])[CH3:14]

Participants

6

Reactant 4

HCID 962WaterHCID 3283Diethyl EtherHCID 6330borane;N-methylmethanamineHCID 59168988(R)-2-((2-methoxy-4-nitrophenoxy)methyl)oxirane

Product 1

HCID 58858089(R)-1-(2-methoxy-4-nitrophenoxy)propan-2-olYield 70.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 160 mL of Et2O cooled to 0° C. was added LiClO4 (80 g; 752 mmol) in portions over 20 min. The mixture was allowed to warm to rt and (R)-2-((2-methoxy-4-nitrophenoxy)methyl)oxirane (9.55 g; 42.5 mmol) was added. The suspension was stirred for 10 min, borane dimethylamine (3.40 g; 46.6 mmol) was added and the suspension was stirred at rt for 2.5 h. The suspension was diluted with CH2Cl2 and stirred in a beaker with H2O until gas evolution ceased. The organic layer was washed with H2O, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was triturated in CH2Cl2, filtered and the filtrate purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 100:0 gradient) to afford 6.83 g (70%) of the title compound as a yellow solid. 1H NMR (CDCl3) δ 1.31 (d, J=6.59 Hz, 3H), 2.77 (br s, 1H), 3.90-3.94 (m, 4H), 4.05-4.08 (m, 1H), 4.24-4.32 (m, 1H), 6.92 (d, J=9.35 Hz, 1H), 7.74 (d, J=2.75 Hz, 1H), 7.88 (dd, J=8.79 Hz, 2.74 Hz, 1H); 13C NMR (CDCl3) δ 18.64, 56.18, 65.87, 74.85, 106.73, 111.66, 117.60, 141.76, 149.20, 153.63; HPLC (Method #1) 2.17 min retention time; LCMS (ES): m/z 228 [M+H]+.

Workup

  1. stirringthe suspension was stirred at rt for 2.5 h
  2. washThe organic layer was washed with H2O
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customThe residue was triturated in CH2Cl2
  7. filtrationfiltered
  8. customthe filtrate purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 100:0 gradient)

Sources & evidence

ORD record
ord-398b2eab9038412aa07ad575754ed896
Source dataset
uspto-grants-2013_12
Patent number
US08618115B2

Reaction notes

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