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

HRID 421497Notes

Reaction equation

HRID 421497 reaction equation
[CH:1]1([NH2:5])[CH2:4][CH2:3][CH2:2]1.C(O)(=O)C.C([BH3-])#N.[Na+].[CH2:14]([O:16][C:17](=[O:27])[C:18]([CH:25]=O)([CH3:24])[CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])[CH3:15]>C(O)C>[CH2:14]([O:16][C:17](=[O:27])[C:18]([CH2:24][NH:5][CH:1]1[CH2:4][CH2:3][CH2:2]1)([CH3:25])[CH2:19][CH2:20][CH:21]([CH3:22])[CH3:23])[CH3:15]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 75645CyclobutylamineHCID 5003444Sodium cyanoborohydrideHCID 574461632-Formyl-2,5-dimethyl-hexanoic acid ethyl ester

Product 1

HCID 58000285Rac-2-cyclobutylaminomethyl-2,5-dimethyl-hexanoic acid ethyl esterYield 48%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

Cyclobutylamine (1.23 mL, 14.4 mmol), glacial acetic acid (1.5 mL), and sodium cyanoborohydride (1.81 g, 28.8 mmol) were added sequentially to a solution of crude rac-2-formyl-2,5-dimethyl-hexanoic acid ethyl ester (prepared as described in Example 19c; 2.88 g, 14.4 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-cyclobutylaminomethyl-2,5-dimethyl-hexanoic acid ethyl ester (1.76 g, 6.89 mmol, 48%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 0.87 (3H, d, J=3.0 Hz), 0.88 (3H, d, J=4.0 Hz), 0.99-1.07 (1H, m), 1.17 (3H, s), 1.26 (3H, t, J=7.5 Hz), 1.42-1.68 (4H, m), 2.43 (1H, d, J=11.7 Hz), 2.73 (1H, d, J=11.7 Hz), 3.15-3.23 (1H, m), 4.13 (2H, q, J=7.0 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-5c3d2af7b8ec427bb3be6d0a0b29eb21
Source dataset
uspto-grants-2012_01
Patent number
US08097613B2

Reaction notes

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