Sulfuric Acid → Ethyl 5-(phenylmethoxy)-1H-indole-2-carboxylate

HRID 1526412Notes

Reaction equation

HRID 1526412 reaction equation
S(=O)(=O)(O)O.Cl.[CH2:7]([O:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21]N)=[CH:17][CH:16]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O=[C:24]([CH3:30])[C:25]([O:27][CH2:28][CH3:29])=[O:26]>C(O)C>[CH2:7]([O:14][C:15]1[CH:20]=[C:19]2[C:18](=[CH:17][CH:16]=1)[NH:21][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:30]2)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 12041Ethyl pyruvateHCID 3016725(4-(Benzyloxy)phenyl)hydrazine monohydrochloride

Product 1

HCID 95721Ethyl 5-(phenylmethoxy)-1H-indole-2-carboxylateYield 69%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Conditions

Temperature
45 °C

Procedure

To a mixture of sulfuric acid (80.0 mL, 1.50 mol) dissolved in Ethanol (450 mL) at 0° C. was added (4-(benzyloxy)phenyl)hydrazine hydrochloride (90.0 g, 359 mmol) to form a suspension. To the suspension was added ethyl 2-oxopropanoate (43.9 mL, 395 mmol) in EtOH (90 mL) and mechanically stirred for 2 h using a mechanical stirrer. The mixture was heated to 45° C. and maintained for 16 h. The mixture was cooled to room temperature and cold EtOH (200 mL) was added. The mixture was filtered through a course frit. The collected solid was washed sequentially with cold EtOH, hexanes, and water. The solid was dried in a vacuum oven (45° C., 2 Ton) to give ethyl 5-(benzyloxy)-1H-indole-2-carboxylate (73.1 g, 247 mmol, 69% yield). Exact mass calculated for C18H17NO3: 295.1, found: LCMS m/z=296.2, [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.41 (t, J=7.1 Hz, 3 H), 4.40 (q, J=7.1 Hz, 2 H), 5.10 (s, 2 H), 7.08 (dd, J1=8.9, J2=2.4 Hz, 1 H), 7.14 (d, J=1.6 Hz, 1 H), 7.20 (d, J=2.3 Hz, 1 H), 7.32 (m, 2 H), 7.39 (m, 2 H), 7.47 (m, 2 H), 8.75 (bs, 1 H).

Workup

  1. customto form a suspension
  2. temperaturemaintained for 16 h
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationThe mixture was filtered through a course frit
  5. washThe collected solid was washed sequentially with cold EtOH, hexanes, and water
  6. customThe solid was dried in a vacuum oven (45° C., 2 Ton)

Sources & evidence

ORD record
ord-20e3e2b8ec4e41a4b048424f247553ff
Source dataset
uspto-grants-2015_07
Patent number
US09085581B2

Reaction notes

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