Acetic Acid → 2-[(4-Fluoro-benzylamino)-methyl]-2,5-dimethyl-hexanoic acid ethyl ester

HRID 1172386Notes

Reaction equation

HRID 1172386 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[C:5]([CH:12]=O)([CH3:11])[CH2:6][CH2:7][CH:8]([CH3:10])[CH3:9])[CH3:2].[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20][NH2:21])=[CH:18][CH:17]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C>[CH2:1]([O:3][C:4](=[O:14])[C:5]([CH2:12][NH:21][CH2:20][C:19]1[CH:22]=[CH:23][C:16]([F:15])=[CH:17][CH:18]=1)([CH3:11])[CH2:6][CH2:7][CH:8]([CH3:10])[CH3:9])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 673264-FluorobenzylamineHCID 5003444Sodium cyanoborohydrideHCID 574461632-Formyl-2,5-dimethyl-hexanoic acid ethyl ester

Product 1

HCID 576066012-[(4-Fluoro-benzylamino)-methyl]-2,5-dimethyl-hexanoic acid ethyl esterYield 49.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (126 mg, 0.629 mmol) in ethanol (3 mL) was treated with 4-fluorobenzylamine (87 mg, 0.692 mmol) and stirred at 60° C. for 18 h. The reaction mixture was allowed to cool to 25° C. and treated with glacial acetic acid (0.036 mL, 0.629 mmol) followed by sodium cyanoborohydride (48 mg, 1.26 mmol). The reaction was stirred for 1 h at 25° C., quenched with a 1.0 M aqueous sodium hydroxide solution (2 mL), extracted with ethyl acetate (2×100 mL), washed with brine (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The crude oil was purified by flash column chromatography (ISCO RediSep column, 0 to 40% ethyl acetate in hexanes) to give 2-[(4-fluoro-benzylamino)-methyl]-2,5-dimethyl-hexanoic acid ethyl ester (96 mg, 49%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.87 (d, 6H, J=6.0 Hz), 1.00-1.14 (m, 2H), 1.17 (s, 3H), 1.24 (t, 3H, J=7.0 Hz), 1.40-1.49 (m, 3H), 1.60 (sextet, 1H, J=6.1 Hz), 2.65 (dd, 2H, J1=108.4 Hz, J2=11.7, Hz), 3.74 (s, 2H), 4.12 (q, 2H, J=7.1 Hz), 6.98 (t, 2H, J=8.6 Hz), 7.26 (q, 2H, J=4.7 Hz). LC-MS (ESI) calculated for C18H28FNO2: 309.4, found 310.3 [M+H+].

Workup

  1. temperatureto cool to 25° C.
  2. stirringThe reaction was stirred for 1 h at 25° C.
  3. customquenched with a 1.0 M aqueous sodium hydroxide solution (2 mL)
  4. extractionextracted with ethyl acetate (2×100 mL)
  5. washwashed with brine (100 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude oil was purified by flash column chromatography (ISCO RediSep column, 0 to 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-ed6a6112f44546dcadee54aebd5881c7
Source dataset
uspto-grants-2010_11
Patent number
US07834009B2

Reaction notes

Loading…