2-Aminophenol → (4-Benzooxazol-2-ylmethyl-phenyl)-methanol

HRID 384508Notes

Reaction equation

HRID 384508 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1.[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1O.C(N1C=CN=C1)(N1C=CN=C1)=O>C1COCC1>[O:12]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[C:10]1[CH2:9][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][OH:1])=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 58012-AminophenolHCID 682631,1'-CarbonyldiimidazoleHCID 32834984-(Hydroxymethyl)phenylacetic acid

Product 1

HCID 67207309(4-Benzooxazol-2-ylmethyl-phenyl)-methanolYield 20.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of (4-hydroxymethyl-phenyl)-acetic acid (5.0 g, 30.1 mmol) and 2-amino-phenol (6.6 g, 60.2 mmol) was heated at 180° C. for 3 h. The crude residue was cooled and then dissolved in THF (50 mL). The resulting solution was treated with carbonyldiimidazole (3.7 g, 22.5 mmol) and stirred at 80° C. for 72 h. The reaction mixture was then partitioned between EtOAc (200 mL) and water (200 mL). The organic layer was dried (MgSO4), filtered and concentrated. Purification by silica gel flash chromatography (0% to 80% EtOAc in hexanes) followed by a second silica gel flash chromatography (0% to 10% CH3OH in CH2Cl2) afforded a colorless oil. The crude oil was then partitioned between EtOAc (200 mL) and 1 N NaOH (200 mL). The organic layer was dried (MgSO4), filtered and concentrated to afford the title compound as a colorless oil (1.5 g, 20%). MS (ESI): mass calcd. for C15H13NO2, 239.09; m/z found, 240.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.70-7.68 (m, 1H), 7.49-7.46 (m, 1H), 7.40-7.35 (m, 4H), 7.33-7.29 (m, 2H), 4.69 (br d, J=4.5 Hz, 2H), 4.28 (s, 2H).

Workup

  1. customThe reaction mixture was then partitioned between EtOAc (200 mL) and water (200 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by silica gel flash chromatography (0% to 80% EtOAc in hexanes)
  6. customafforded a colorless oil
  7. customThe crude oil was then partitioned between EtOAc (200 mL) and 1 N NaOH (200 mL)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b63f19a94081497485f7962f83641498
Source dataset
uspto-grants-2013_02
Patent number
US08367719B2

Reaction notes

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