Triethylamine → (4-{4-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-phenyl}-cyclohexyl)-acetic acid ethyl ester

HRID 631936Notes

Reaction equation

HRID 631936 reaction equation
[CH2:1]([O:3][C:4]([CH2:6][CH:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:23]=[N:22][N:21]([CH3:24])[C:20]=3C(O)=O)=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)=[O:5])[CH3:2].C([N:30]([CH2:33]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:42])C=CC=CC=1.[C:52]1([C@H:58]([OH:60])[CH3:59])[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:5])[CH2:6][CH:7]1[CH2:8][CH2:9][CH:10]([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[N:23]=[N:22][N:21]([CH3:24])[C:20]=3[NH:30][C:33]([O:60][C@@H:58]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[CH3:59])=[O:42])=[CH:17][CH:18]=2)[CH2:11][CH2:12]1)[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 6375161-Phenylethanol, (R)-HCID 715005385-[4-(4-ethoxycarbonylmethyl-cyclohexyl)-phenyl]-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid

Product 1

HCID 118061991(4-{4-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-phenyl}-cyclohexyl)-acetic acid ethyl esterYield 35%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
81 °C

Procedure

To a light brown solution of 5-[4-(4-ethoxycarbonylmethyl-cyclohexyl)-phenyl]-3-methyl-3H-[1,2,3]triazole-4-carboxylic acid (37 mg, 0.099 mmol) in toluene (5 mL) was added triethylamine (20.2 mg, 27.8 μL, 0.199 mmol) at room temperature. To the resulting solution was added diphenylphosphoryl azide (30.2 mg, 23.6 μL, 0.11 mmol) followed by (R)-1-phenylethanol (13.4 mg, 13.2 μL, 0.11 mmol) at room temperature. The resulting solution was heated with oil bath to 81° C. and stirred for 1 h at which time TLC analysis indicated the absence of the starting material. Then, the reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The crude residue was treated with dichloromethane (10 mL) and filtered. The filtrate was loaded onto an ISCO (40 g) column chromatography eluting with ethyl acetate in hexanes (0-100%). The desired fractions were combined and the solvent was removed under vacuum to obtain (4-{4-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-phenyl}-cyclohexyl)-acetic acid ethyl ester (17 mg, 35% yield) as a white solid. LC/MS calcd for C28H34N4O4 (m/e) 490, obsd. 491.3 [M+H, ES+].

Workup

  1. temperatureThen, the reaction mixture was cooled to room temperature
  2. customthe solvent was removed under vacuum
  3. additionThe crude residue was treated with dichloromethane (10 mL)
  4. filtrationfiltered
  5. washeluting with ethyl acetate in hexanes (0-100%)
  6. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-4c6b4f09cac04491b5ac7a258fa6c796
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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