Ethyl 2-formylcyclopropanecarboxylate → HCID 57554524, compound

HRID 551968

Reaction equation

HRID 551968 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:31]=[CH:30][C:16]([CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]([F:29])=[C:23]([CH:28]=3)[C:24]([O:26][CH3:27])=[O:25])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[CH2:32]([O:34][C:35]([CH:37]1[CH2:39][CH:38]1[CH:40]=O)=[O:36])[CH3:33].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C([O-])(O)=O.[Na+]>ClCCCl>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([CH2:17][N:18]([CH2:40][CH:38]3[CH2:39][CH:37]3[C:35]([O:34][CH2:32][CH3:33])=[O:36])[C:19]3[CH:20]=[CH:21][C:22]([F:29])=[C:23]([CH:28]=3)[C:24]([O:26][CH3:27])=[O:25])=[CH:30][CH:31]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 89334Ethyl 2-formylcyclopropanecarboxylateHCID 516892Sodium BicarbonateHCID 2724942TriacetoxyborohydrideHCID 11452740Methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate

Product 1

HCID 57554524HCID 57554524, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

To solution of methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate (500 mg; 1.20 mmol) in anhydrous DCE (30 mL) were added ethyl-2-formyl-1-cyclopropanecarboxylate (Aldrich, 0.40 mL; 3.01 mmol), triacetoxyborohydride (382 mg; 1.81 mmol).The resulting mixture was stirred at 50° C. under N2 atmosphere for 4 hours. The mixture was poured into a saturated solution of NaHCO3 (50 mL) and extracted with DCM (2×50 mL). The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate, filtrated and the solvents were removed under reduced pressure to give 872 mg. Purification of this crude by flash chromatography on silicagel (c-Hex/EtOAc, gradient 95:5 to 90:10) gave 340 mg (65%) of the title compound as a yellow oil. HPLC, Rt: 6.06 min (purity=96.2%). LC/MS, M+(ESI): 542.3. 1H NMR (CDCl3) δ: 7.43 (t, J=8.5 Hz, 4H), 7.32 (m, 1H), 7.22 (d, J=7.9 Hz, 2H), 7.15 (d, J=7.9 Hz, 2H), 6.93 (m, 2H), 4.54 (s, 2H), 4.08 (m, 2H), 3.89 (s, 3H), 3.35 (m, 2H), 2.61 (t, J=7.5 Hz, 2H), 1.32-1.58 (m, 7H), 1.24 (t, J=7.0 Hz, 3H), 0.92 (t, J=7.3 Hz, 3H), 0.88 (m, 1H).

Workup

  1. customresulting mixture
  2. extractionextracted with DCM (2×50 mL)
  3. washThe combined organic layers were washed with brine (100 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltrated
  6. customthe solvents were removed under reduced pressure
  7. customto give 872 mg
  8. customPurification of this crude by flash chromatography on silicagel (c-Hex/EtOAc, gradient 95:5 to 90:10)

Sources & evidence

ORD record
ord-7edda0d8f6b84f76a63ee1578a022afe
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Linked notes

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