Acetic Acid → Rac-2-cyclopropylaminomethyl-2,5-dimethyl-hexanoic acid ethyl ester

HRID 1516010Notes

Reaction equation

HRID 1516010 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.C(O)(=O)C.C([BH3-])#N.[Na+].[CH2:13]([O:15][C:16](=[O:26])[C:17]([CH:24]=O)([CH3:23])[CH2:18][CH2:19][CH:20]([CH3:22])[CH3:21])[CH3:14]>C(O)C>[CH2:13]([O:15][C:16](=[O:26])[C:17]([CH2:23][NH:4][CH:1]1[CH2:3][CH2:2]1)([CH3:24])[CH2:18][CH2:19][CH:20]([CH3:21])[CH3:22])[CH3:14]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 69828CyclopropylamineHCID 5003444Sodium cyanoborohydrideHCID 574461632-Formyl-2,5-dimethyl-hexanoic acid ethyl ester

Product 1

HCID 58000164Rac-2-cyclopropylaminomethyl-2,5-dimethyl-hexanoic acid ethyl esterYield 38.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

Cyclopropylamine (1.00 mL, 14.4 mmol), glacial acetic acid (1.0 mL), and sodium cyanoborohydride (1.82 g, 29.0 mmol) were added sequentially to a solution of crude rac-2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (2.90 g, 14.5 mmol) in ethanol (40 mL) at 25° C. The mixture was stirred at 25° C. for 18 h, and then was concentrated in vacuo. The residue was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was purified by flash column chromatography (self-packed glass column, gradient elution: 20-30% ethyl acetate in hexanes) to afford rac-2-cyclopropylaminomethyl-2,5-dimethyl-hexanoic acid ethyl ester (1.33 g, 5.51 mmol, 38%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 0.00-0.04 (2H, m), 0.12-0.16 (2H, m), 0.62 (6H, d, J=6.4 Hz), 0.76-0.86 (1H, m), 0.88 (3H, s), 1.00 (3H, t, J=6.9 Hz), 1.12-1.25 (2H, m), 1.30-1.38 (2H, m), 1.82-1.87 (1H, m), 2.38 (1H, d, J=11.7 Hz), 2.67 (1H, d, J=11.9 Hz), 3.86 (2H, q, J=6.9 Hz).

Workup

  1. concentrationwas concentrated in vacuo
  2. customThe residue was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (2×150 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationwere concentrated in vacuo
  5. customThe residue was purified by flash column chromatography (self-packed glass column, gradient elution: 20-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-4e8b1472fc0a49869df379b32e80422b
Source dataset
uspto-grants-2012_07
Patent number
US08222404B2

Reaction notes

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