Diisopropylethylamine → HCID 14805857, compound

HRID 588911Notes

Reaction equation

HRID 588911 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:9])[C:5]([NH2:8])([CH3:7])[CH3:6].C(N(CC)C(C)C)(C)C.[C:19]([O:23][C:24]([NH:26][C:27]([CH3:32])([CH3:31])[C:28](O)=[O:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:2][O:3][C:4](=[O:9])[C:5]([CH3:7])([CH3:6])[NH:8][C:28](=[O:29])[C:27]([CH3:32])([CH3:31])[NH:26][C:24]([O:23][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:25]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 27960291-Hydroxybenzotriazole hydrateHCID 13258034Methyl 2-aminoisobutyrate hydrochloride

Product 1

HCID 14805857HCID 14805857, compoundYield 75.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Aminoisobutyric acid methyl ester hydrochloride 2 (11.44 g, 74.47 mmol) and N,N-diisopropylethylamine (9.63 g, 74.5 mmol) were dissolved in DMF (400 mL) and the solution added to solid N-tert-butoxycarbonyl α,α-dimethylglycine (15.14 g, 74.49 mmol). The solution/suspension was cooled to 0° C. (icebath) and HOBt hydrate (11.41 g, 74.51 mmol) and then EDC hydrochloride (15.71 g, 81.95 mmol) added together with more DMF (100 mL). The reaction mixture was stirred for 30 min at 0° C., after which the icebath was removed and stirring continued for 66 h at room temperature. The solvent was evaporated and the residue taken up in EtOAc (500 mL). The solution was washed with 2 M HCl (3×175 mL), 7.5% (w/w) K2CO3 solution (3×175 mL) and saturated brine (175 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a slightly yellowish solid (17.04 g). The solid (16.72 g) was washed with hexane (4×70 mL) affording an off-white solid (14.72 g, 67%), with spectral characteristics in accordance with literature data2,3; 1H NMR (200 MHz; DMSO-d6) δ 7.57 (s, 1H, NH(Aib2)), 6.63 (br s, 1H, NH(Aib1)), 3.55 (s, 3H, OCH3), 1.37 (s, 9H, (CH3)3), 1.34 (s, 6H, CH3), 1.28 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 174.5, 174.0, 154.1, 78.0, 55.5, 55.1, 51.7, 28.1, 24.8, 24.7; HRMS (m/z): [M+Na]+ calcd. for C14H26N2O5Na, 325.1739. found, 325.1746; Anal. Calcd. for C14H26N2O5: C, 55.61; H, 8.67; N, 9.26. Found: C, 55.9; H, 8.7; N, 9.2.

Workup

  1. customafter which the icebath was removed
  2. stirringstirring
  3. waitcontinued for 66 h at room temperature
  4. customThe solvent was evaporated
  5. washThe solution was washed with 2 M HCl (3×175 mL), 7.5% (w/w) K2CO3 solution (3×175 mL) and saturated brine (175 mL)
  6. dry with materialThe solution was dried with anhydrous MgSO4
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-ce8d8dba99b6450688c2dc6c6e0bd29a
Source dataset
uspto-grants-2016_01
Patent number
US09227995B2

Reaction notes

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