Pyrophosphoric acid → HCID 66964436, compound

HRID 1630685Notes

Reaction equation

HRID 1630685 reaction equation
C(O)(=O)/C=C/C(O)=O.[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[CH:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:19][CH2:18][N:17]([CH3:27])[CH2:16][C:15]=2[CH:28]=1.P(OP(O)(O)=O)(O)(O)=O.[OH-].[NH4+]>ClCCCl>[CH3:9][O:10][C:11]1[C:28]2[CH:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:19][CH2:18][N:17]([CH3:27])[CH2:16][C:15]=2[CH:14]=[CH:13][CH:12]=1.[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[CH:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:19][CH2:18][N:17]([CH3:27])[CH2:16][C:15]=2[CH:28]=1

Participants

6

Reactant 3

HCID 1023Pyrophosphoric acidHCID 14923Ammonium HydroxideHCID 131728949HCID 131728949, compound

Product 2

HCID 66964436HCID 66964436, compoundYield 35%HCID 66964783HCID 66964783, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of the product from step A (1.0 g, 3.74 mmol) and pyrophosphoric acid (25 g) in 1,2-dichloroethane (5 mL) was heated at 100° C. for 1 hour. The reaction mixture was cooled, mixed with ice and adjusted to pH 9 with ammonium hydroxide. The reaction mixture was extracted with ethyl acetate (3×). The combined extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. Purification via MPLC (30% to 50% ethyl acetate/hexanes) provided 6-methoxy-2-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepine (350 mg, 35%) and 8-methoxy-2-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepine (280 mg, 28%); 6-methoxy-2-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepine: 1H NMR (CDCl3, 300 MHz) δ 7.28-7.21 (m, 2H), 7.19-7.13 (m, 2H), 7.06 (d, J=8.0 Hz, 2H), 6.85 (d, J=8.1 Hz, 1H), 6.80 (d, J=7.5 Hz, 1H), 5.12 (t, J=4.9 Hz, 1H), 3.82 (d, J=14.3 Hz, 1H), 3.72 (s, 3H), 3.45 J=13.6 Hz, 1H), 2.92-2.85 (m, 1H), 2.75-2.70 (m, 1H), 2.34-2.29 (m, 2H), 2.27 (s, 3H); ESI MS m/z=268 [M+H]+; 8-methoxy-2-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepine: 1H NMR (CDCl3, 500 MHz) δ 7.34 (t, J=7.5 Hz, 2H), 7.26-7.23 (m, 1H), 7.17 (d, J=7.5 Hz, 2H), 6.74 (d, J=2.7 Hz, 1H), 6.61-6.59 (m, 2H), 4.26 (d, J=8.6 Hz, 1H), 3.91-3.90 (m, 1H), 3.76 (s, 3H), 3.70 (d, J=14.1 Hz, 1H), 3.12-3.09 (m, 1H), 2.98-2.93 (m, 1H), 2.35 (s, 3H), 2.32-2.27 (m, 1H), 2.11-2.10 (m, 1H). ESI MS m/z=268 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. additionmixed with ice
  3. extractionThe reaction mixture was extracted with ethyl acetate (3×)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customPurification via MPLC (30% to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-3f1c6d40a7bc46a48acc4c1cbd665105
Source dataset
uspto-grants-2014_07
Patent number
US08791101B2

Reaction notes

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