Benzaldehyde → HCID 10192809, compound

HRID 735271Notes

Reaction equation

HRID 735271 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]([C@@H:7]([NH2:11])[C:8]([OH:10])=O)=[CH:5][CH:6]=1.[CH3:12][NH-:13].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OCC)(=O)C>CO>[CH3:12][N:13]1[C:8](=[O:10])[C@@H:7]([C:4]2[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=2)[NH:11][C@H:14]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 8857Ethyl AcetateHCID 521998p-Toluenesulfonic acid monohydrateHCID 86590321HCID 86590321, compound

Product 1

HCID 10192809HCID 10192809, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (R)-phenylglycine methyl amide (2.0 g, 12.2 mmol), benzaldehyde (990 μL, 9.7 mmol), and p-toluenesulfonic acid monohydrate (232 mg, 1.2 mmol) dissolved in 20 mL of methanol was heated to reflux for 16 hours. Concentration of the reaction mixture followed by silica gel chromatography (30-40% ethyl acetate in hexanes, linear gradient) afforded the title compound in 31% yield (750 mg, 3.0 mmol) and the more quickly eluting (2S, 5R) isomer in 58% yield (1.43 g, 5.7 mmol). IR (film) 3478, 3324, 3086, 3063, 3031, 2958, 2917, 2863, 1959, 1890, 1814, 1698, 1603, 1477, 1456, 1428, 1400, 1343, 1281, 1204, 1107, 1069, 1027, 985.9, 935.2, 916.7, 868.6, 834.7, 732.9, 698.1 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.41 (m, 10H, ArH), 5.33 (s, 1H, NCHN), 4.66 (s, 1H, CHCO), 2.65 (s, 3H, CH3), 2.46 (s, 1H, NH); 13C NMR (75 MHz, CDCl 3) δ 173.4, 139.0, 138.6, 129.8, 129.3, 128.9, 128.3, 128.0, 127.7, 77.3, 63.7, 28.0; HRMS (CI) exact mass calc'd for (C16H16N2O) requires m/z 252.1263, found m/z 252.1265. [α]D=−8.6 (c=1.0, CHCl3). The relative stereochemistry of catalyst 3 was confirmed by NOE studies.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 hours

Sources & evidence

ORD record
ord-5e2079f5eae749e3842411a9e6412391
Source dataset
uspto-grants-2009_09
Patent number
US07592463B2

Reaction notes

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