Triethyl orthoacetate → 2-(2-Pentyl-benzoxazol-5-yl)-ethanol

HRID 1170413Notes

Reaction equation

HRID 1170413 reaction equation
[CH2:1]([C:6]1[O:7][C:8]2[CH:14]=[CH:13][C:12]([CH2:15][C:16](O)=[O:17])=[CH:11][C:9]=2[N:10]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C(OCC)(OCC)(OCC)C.C(=O)([O-])O.[Na+]>CCOC(C)=O>[CH2:1]([C:6]1[O:7][C:8]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][OH:17])=[CH:11][C:9]=2[N:10]=1)[CH2:2][CH2:3][CH2:4][CH3:5]

Participants

5

Reactant 3

HCID 66221Triethyl orthoacetateHCID 516892Sodium BicarbonateHCID 68767623(2-Pentyl-benzoxazol-5-yl)-acetic acid

Product 1

HCID 687698612-(2-Pentyl-benzoxazol-5-yl)-ethanol

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (2-pentyl-benzoxazol-5-yl)-acetic acid (2.11 g, 8.53 mmol) in triethyl orthoacetate (4.67 ml, 25.6 mmol) was heated under pressure (in three portions in the microwave Emrys optimizer) to 180° C. for 8 minutes. After cooling to RT the reaction mixture was distributed between AcOEt and saturated aqueous sodium hydrogen carbonate. The organic layer was washed two times with water, dried over MgSO4 and concentrated in vacuum. 1.88 g of the crude (2-pentyl-benzoxazol-5-yl)-acetic acid ethyl ester (2.31 g, 99%) were dissolved in dry ethanol (43 ml) and added to a solution of Ca(BH4)2 (prepared from sodium borohydride (3.87 g, 102.4 mmol) suspended in dry ethanol (130 ml), cooled to −10° C., treated with CaCl2 (5.68 g, 51.2 mmol) and stirred for 45 minutes while warming to 0° C.). After stirring for 2 hours at 8° C. the reaction mixture was filtered and the precipitate washed with ethanol. The filtrate was combined with the washings and concentrated in vacuum, treated with MeOH and concentrated again. Silica gel chromatography (eluent: DCM/methanol 10/1) provided the title compound as colorless solid. 1H-NMR (DMSO-d6) δ: 7.51 (d, J=8.1 Hz; 1H), 7.49 (s; 1H), 7.16 (dd, J=8.3, 1.6 Hz; 1H), 4.60 (t, J=5.2 Hz; 1H), 3.61 (m; 2H), 2.88 (t, J=7.4 Hz; 2H), 2.80 (t, J=7.0 Hz; 2H), 1.76 (m; 2H), 1.30 (m; 4H), 0.85 (m; 3H).

Workup

  1. washThe organic layer was washed two times with water
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuum
  4. dissolution1.88 g of the crude (2-pentyl-benzoxazol-5-yl)-acetic acid ethyl ester (2.31 g, 99%) were dissolved in dry ethanol (43 ml)
  5. filtrationwas filtered
  6. washthe precipitate washed with ethanol
  7. concentrationconcentrated in vacuum
  8. additiontreated with MeOH
  9. concentrationconcentrated again

Sources & evidence

ORD record
ord-123e267a58af42589d421196839544ab
Source dataset
uspto-grants-2010_11
Patent number
US07825260B2

Reaction notes

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