1,2-Dimethoxyethane → HCID 22396623, compound

HRID 1356340Notes

Reaction equation

HRID 1356340 reaction equation
Br[C:2]1[C:3]2[C:4]3[CH2:15][CH2:14][N:13]([C:16]([O:18]C(C)(C)C)=O)[CH2:12][CH2:11][C:5]=3[NH:6][C:7]=2[CH:8]=[CH:9][CH:10]=1.[CH2:23]([CH2:26][O:27][CH3:28])OC.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C.CCCCCC>[C:16]([N:13]1[CH2:14][CH2:15][C:4]2[C:3]3[C:2]([C:23]4[CH:11]=[CH:5][CH:4]=[CH:15][C:26]=4[O:27][CH3:28])=[CH:10][CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:11][CH2:12]1)(=[O:18])[C:2]1[CH:3]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 3

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 22396611HCID 22396611, compound

Product 1

HCID 22396623HCID 22396623, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21226206Ethyl acetate hexaneSolvent

Procedure

tert-Butyl 10-bromo-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (4.40 g, 11.9 mmol), Pd(PPh3)4 (1.40 g, 1.21 mmol), and dimethoxyethane (60 mL) were stirred at room temperature for 15 minutes then treated with 2-methoxyboronic acid (2.18 g, 14.3 mmol) and a 2 M solution of Na2CO3 (36 mL). The reaction was heated to reflux for 17.0 hours then cooled to room temperature and partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (2×) and the organic layers were combined, washed with brine, dried over MgSO4 and concentrated in vacuo to give a brown foam which was passed through a column of silica gel with 40% ethyl acetate/hexane to give 3.87 g (82%) of a white solid as the title compound: mp 218.9-221.6° C. 1H NMR (400 MHz, DMSO-d6) δ 10.95-10.85 (m, 1H), 7.43-7.38 (m, 4H), 7.27-7.23 (m, 2H), 7.17-6.97 (m, 4H), 6.67-6.61 (m, 1H), 3.82 (m, 1H), 3.66-3.53 (m, 5H), 3.27 (m, 1H), 3.09-3.06 (m, 1H), 2.85 (m, 1H), 2.39-2.32 (m, 1H), 2.17-2.13 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ 170.1, 169.8, 156.8, 156.7, 137.1, 135.7, 134.8, 134.6, 130.8, 130.5, 130.4, 130.2, 130.0, 128.9, 128.5, 128.3, 128.2, 126.1, 126.0, 120.5, 119.9, 119.8, 119.7, 111.2, 110.5, 110.2, 109.7, 109.5, 54.9, 54.7, 49.6, 48.3, 46.1, 44.2, 29.4, 27.5, 25.7, 24.6; IR (diffuse reflectance) 3202, 3181 (b), 1602 (s), 1500, 1489, 1466, 1434, 1299, 1266, 1249, 1241, 786, 759 (s), 748, 707 cm−1; HRMS (FAB) calcd for C26H24N2O2+H1 397.1916, found 397.1910. Anal. Calcd for C26H24N2O2: C, 78.76; H, 6.10; N, 7.07. Found: C, 78.40; H, 6.22; N, 6.97.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 17.0 hours
  3. custompartitioned between ethyl acetate and water
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto give a brown foam which

Sources & evidence

ORD record
ord-f16f19bbef7a4cd89df79cc97dcba677
Source dataset
uspto-grants-2003_07
Patent number
US06586421B2

Reaction notes

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