Ethyl trifluoroacetate → HCID 178471761, compound

HRID 2042725Notes

Reaction equation

HRID 2042725 reaction equation
[F:1][C:2]([F:9])([F:8])[C:3](OCC)=O.[O-]CC.[Na+].[C:14]([C:17]1[CH:22]=[CH:21][C:20]([C@H:23]2[CH2:28][CH2:27][C@H:26]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:25][CH2:24]2)=[CH:19][CH:18]=1)(=O)[CH3:15].O.[NH2:36][NH2:37]>C(OC)(C)(C)C>[F:1][C:2]([F:9])([F:8])[C:3]1[NH:37][N:36]=[C:14]([C:17]2[CH:22]=[CH:21][C:20]([C@H:23]3[CH2:28][CH2:27][C@H:26]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:25][CH2:24]3)=[CH:19][CH:18]=2)[CH:15]=1

Participants

6

Reactant 4

HCID 9794Ethyl trifluoroacetateHCID 24654Hydrazine hydrate (1:1)HCID 2723922Sodium ethoxideHCID 178471767HCID 178471767, compound

Product 1

HCID 178471761HCID 178471761, compound

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent2×

Conditions

Temperature
70 °C

Procedure

A 50 mL flask was charged with 6.6 mL methyl tert-butyl ether and ethyl trifluoroacetate (520 uL, 3.47 mmol). To this solution was then added 533 μL of sodium ethoxide (21% in ethanol) slowly, followed by the product of Example 26A (1.00 g, 3.47 mmol) in 3 mL of methyl tert-butyl ether over 5 minutes. After stirring overnight, the solution was quenched with sat NH4Cl and extracted with ethyl acetate (×2). The ethyl acetate layers were then evaporated to dryness, and the residue taken up in ethanol (5 mL). Two equivalents of hydrazine hydrate (35% in water) were added, and the solution heated to 70° C. overnight. After this time, the solution was cooled to room temperature and the solvent evaporated in vacuo. The residue was taken up in 1:1 methanol/DMSO and purified over RP-HPLC to afford the title product. 1H NMR (300 MHz, DMSO-D6) δ ppm 1.03-1.15 (m, 1 H), 1.19 (t, J=7.12 Hz, 3 H), 1.37-1.60 (m, 2 H), 1.69-1.86 (m, 5 H), 2.15-2.27 (m, 2 H), 4.07 (q, J=7.12 Hz, 2 H), 6.96-7.22 (m, 1 H), 7.26-7.43 (m, 2 H), 7.63-7.80 (m, 2 H), 13.98 (s, 1H): MS (ESI) m/z 381 [M+H]+.

Workup

  1. customthe solution was quenched with sat NH4Cl
  2. extractionextracted with ethyl acetate (×2)
  3. customThe ethyl acetate layers were then evaporated to dryness
  4. temperatureAfter this time, the solution was cooled to room temperature
  5. customthe solvent evaporated in vacuo
  6. custompurified over RP-HPLC

Sources & evidence

ORD record
ord-e64ec29747bb483db24d0edeb88cca51
Source dataset
uspto-grants-2013_11
Patent number
US08586594B2

Reaction notes

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