Triethylamine → N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1-methyl-1H-tetrazol-5-yl)phenethoxy)propanamide

HRID 909904Notes

Reaction equation

HRID 909904 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[CH3:19][O:20][CH:21]([O:30][CH3:31])[CH2:22][NH:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.[CH3:32][N:33]1[C:37]([C:38]2[CH:39]=[C:40]([CH:49]=[CH:50][CH:51]=2)[CH2:41][CH2:42][O:43][CH2:44][CH2:45][C:46](O)=[O:47])=[N:36][N:35]=[N:34]1.C(N(CC)CC)C>C1COCC1.C(#N)C.C(OCC)(=O)C>[CH:24]1([N:23]([CH2:22][CH:21]([O:30][CH3:31])[O:20][CH3:19])[C:46](=[O:47])[CH2:45][CH2:44][O:43][CH2:42][CH2:41][C:40]2[CH:49]=[CH:50][CH:51]=[C:38]([C:37]3[N:33]([CH3:32])[N:34]=[N:35][N:36]=3)[CH:39]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 3024915N-(2,2-dimethoxyethyl)cyclohexanamineHCID 59290395HCID 59290395, compound

Product 1

HCID 59290451N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1-methyl-1H-tetrazol-5-yl)phenethoxy)propanamide

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of T3P (0.52 mL) dissolved in THF (1.57M) was added in one portion to a stirred solution of N-(2,2-dimethoxyethyl)cyclohexanamine (0.09 mL), 3-(3-(1-methyl-1H-tetrazol-5-yl)phenethoxy)propanoic acid [Example 8, Step i)] (0.11 g) and triethylamine (0.69 mL) in acetonitrile (2 mL) at 25° C. The resulting solution was stirred at 25° C. for 15 min. The reaction mixture was diluted with ethyl acetate (50 mL), and washed with saturated sodium hydrogen carbonate (20 mL). The organic was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20-100% ethyl acetate in isohexane to afford the subtitled compound (0.10 g). 1H NMR (400 MHz, CD3OD) δ 7.68 (s, 1H), 7.65-7.60 (m, 1H), 7.54-7.48 (m, 2H), 4.52 and 4.37 (2×t, J=5.3 Hz, 1H), 4.18 and 4.18 (2×s, 3H), 4.05-3.95 and 3.68-3.61 (2×m, 1H), 3.76-3.67 (m, 4H), 3.35 and 3.33 (2×s, 6H), 3.25 (d, J=5.1 Hz, 2H), 2.96 and 2.95 (2×t, J=6.3 Hz, 2H), 2.66 and 2.64 (2×t, J=6.6 Hz, 2H), 1.82-1.04 (m, 10H), a ˜1:1 mixture of rotamers is observed.

Workup

  1. washwashed with saturated sodium hydrogen carbonate (20 mL)
  2. dry with materialThe organic was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 20-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-b90520f15b9d4a3b95cae7034049359a
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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