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

HRID 909902Notes

Reaction equation

HRID 909902 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[N:37]=[N:36][C:35]([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: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:35]3[N:36]=[N:37][N:33]([CH3:32])[N:34]=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 59290424HCID 59290424, compound

Product 1

HCID 59290471N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(2-methyl-2H-tetrazol-5-yl)phenethoxy)propanamide

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of T3P (1.91 mL) dissolved in THF (1.57M) was added in one portion to a stirred solution of N-(2,2-dimethoxyethyl)cyclohexanamine (0.33 mL), 3-(3-(2-methyl-2H-tetrazol-5-yl)phenethoxy)propanoic acid [Example 7, Step iii)] (0.41 g) and triethylamine (2.51 mL) in acetonitrile (5 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 layer 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, then elution gradient 0-10% methanol in ethyl acetate to afford the subtitled compound (0.66 g). 1H NMR (400 MHz, CD3OD) δ 7.97-7.93 (m, 1H), 7.92-7.89 (m, 1H), 7.43-7.33 (m, 2H), 4.52 and 4.36 (2×t, J=5.3 Hz, 1H), 4.40 and 4.39 (2×s, 3H), 4.04-3.95 and 3.69-3.60 (2×m, 1H), 3.75-3.66 (m, 4H), 3.33 (s, 6H), 3.25 (d, J=4.9 Hz, 2H), 2.94-2.88 (m, 2H), 2.67-2.61 (m, 2H), 1.79-1.00 (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 layer 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
  7. washelution gradient 0-10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-3ce2e79ee235408ebe4eb0e55c7b333c
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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