p-Toluenesulfonic acid → Ethyl acetate hexane

HRID 1095210Notes

Reaction equation

HRID 1095210 reaction equation
OCCN[C:5](=[O:10])[C:6](F)(F)F.[C:11]1(C)[CH:16]=[CH:15][C:14](S(O)(=O)=O)=[CH:13][CH:12]=1.C1C[O:25][CH2:24][CH2:23]1>>[C:24]([O:10][CH2:5][CH3:6])(=[O:25])[CH3:23].[CH3:15][CH2:16][CH2:11][CH2:12][CH2:13][CH3:14]

Participants

4

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 8028TetrahydrofuranHCID 95211N-Trifluoroacetyl-2-aminoethanol

Product 1

HCID 21226206Ethyl acetate hexaneYield 48%

Procedure

Aldehyde 6 (2 g, 6.4 mmol, 1 equiv) and N-(2-hydroxyethyl)-2,2,2-trifluoroacetamide (7.37 g, 44.8 mmol, 7 equiv) were dissolved in dry THF (30 mL) followed by addition of p-Toluenesulphonic acid (0.21 g, 1.24 mmol, 0.16 equiv) and 5 Å molecular sieves (30 g). The reaction mixture was stirred overnight and quenched with triethylamine the next day. Molecular sieves from the reaction mixture were removed by filtering with a buckner funnel. A 150 mL portion of water was added to the filtrate and the reaction mixture was extracted with 5×150 mL portion of ethyl acetate. The ethyl acetate was evaporated and the yellow oil was loaded onto the silica gel column. The product was purified by eluting the column with 2/1 hexane/ethyl acetate, 1/1 hexane/ethyl acetate, 1/2 hexane/ethyl acetate and finally with ethyl acetate alone to afford light yellow colored solid. The product was recrystallized twice from ethyl acetate/hexane (1.9 g, 48% yield). Mp: 87.5-88.9° C. IR (cm−1): 3306 (b), 2886 (s), 1714 (s), 1564 (s), 1157 (s). 1H NMR (300 MHz, CDCl3): δ3.34 (s, 3 H), 3.36-3.65 (m, 8 H), 3.71-3.84-3.73 (m, 12 H), 3.79 (t, 2 H, J=4.8), 4.09 (t, 2 H, J=5.2), 5.49 (s, 1 H), 7.1 (m, 3 H,), 7.25 (m, 1 H), 9.85 (s, 1 H). 13C NMR (CDCl3) δ 42.60, 56.12, 61.34, 64.44, 69.31, 70.32, 70.75, 71.07, 71.67, 100.57, 114.82, 117.81, 121.57, 123.05, 129.15, 137.62, 156.40 (q, J=35), 164.2 (s). Calcd: [M+H]+ (C24H35O9F6N2) m/z=609.224. Found FAB-HRMS: [M+H]+=609.2246. Anal. Calcd: C, 47.37; H, 5.63; N, 4.60. Found C, 47.68; H, 5.32; N, 4.53.

Workup

  1. customquenched with triethylamine the next day
  2. customMolecular sieves from the reaction mixture were removed
  3. filtrationby filtering with a buckner funnel
  4. additionA 150 mL portion of water was added to the filtrate
  5. extractionthe reaction mixture was extracted with 5×150 mL portion of ethyl acetate
  6. customThe ethyl acetate was evaporated
  7. customThe product was purified
  8. washby eluting the column with 2/1 hexane/ethyl acetate, 1/1 hexane/ethyl acetate, 1/2 hexane/ethyl acetate
  9. customfinally with ethyl acetate alone to afford light yellow colored solid

Sources & evidence

ORD record
ord-55e02857f2e34f9cb1ec739bdc5bdb34
Source dataset
uspto-grants-2012_03
Patent number
US08137700B2

Reaction notes

Loading…