Acetic Acid → HCID 16737670, compound

HRID 2264540Notes

Reaction equation

HRID 2264540 reaction equation
[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13]([C:15]4[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=4)=[CH:12][C:11]=3[CH:23]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(=O)C.[NH:28]1[CH2:31][CH:30]([C:32]([OH:34])=[O:33])[CH2:29]1.C([BH3-])#N.[Na+]>C(Cl)Cl.CO.CO>[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13]([C:15]4[CH:16]=[CH:17][C:18]([CH2:19][N:28]5[CH2:31][CH:30]([C:32]([OH:34])=[O:33])[CH2:29]5)=[CH:21][CH:22]=4)=[CH:12][C:11]=3[CH:23]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 59595913HCID 59595913, compound

Product 1

HCID 16737670HCID 16737670, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of 4-(5-cyclohexylbenzofuran-2-yl)benzaldehyde (30 mg, 0.1 mmol), acetic acid (9 μL, 0.15 mmol) and azetidine-3-carboxylic acid (15 mg, 0.15 mmol) in DCM/MeOH (1:1, 2 mL) was stirred at room temperature for 1 h. Sodium cyanoborohydride (3.1 mg, 0.05 mmol) was added and the reaction mixture was stirred for 3 h at room temperature. After concentration of solvent under reduced pressure, the resulting residue was dissolved in hot MeOH and filtered. The filtrate and the white solid, which was redisolved in hot DMSO, were both purified by reverse phase preparative HPLC (Phenomenex reverse phase Luna 5μ C18(2) column, 60×21.2 mm ID) to yield the desired final product (16 mg, 42% yield) as a white powder: >95% purity by LCMS, ESI-MS: 459.1 (M+H)+, 1H NMR (400 MHz, CD3OD) δ 7.95 (d, 2H), 7.56 (d, 2H), 7.45 (d, 1H), 7.42 (d, 1H), 7.24 (s, 1H), 7.19 (dd, 1H), 4.45 (s, 2H), 4.34 (dd, 4H), 3.69 (m, 1H), 2.64-2.57 (d, 1H), 1.89 (t, 4H), 1.58-1.40 (m, 4H), 1.38-1.26 (m, 2H).

Workup

  1. stirringthe reaction mixture was stirred for 3 h at room temperature
  2. filtrationfiltered
  3. customboth purified by reverse phase preparative HPLC (Phenomenex reverse phase Luna 5μ C18(2) column, 60×21.2 mm ID)

Sources & evidence

ORD record
ord-b7a0d1ae211e44dc8729a33b4f1a939a
Source dataset
uspto-grants-2010_12
Patent number
US07855193B2

Reaction notes

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