Acetic Acid → HCID 90388177, compound

HRID 874463Notes

Reaction equation

HRID 874463 reaction equation
[CH3:1][N:2]1[C:15]2[C:6]([CH:7]=[CH:8][C:9]3[NH:19][CH2:18][CH:17]=[C:11]4[NH:12][C:13](=[O:16])[C:14]=2[C:10]=34)=[C:5]([CH2:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:4]=[CH:3]1.O=[C:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1.ClC(Cl)C.C(O)(=O)C.[Na]>>[CH3:1][N:2]1[C:15]2[C:6]([CH:7]=[CH:8][C:9]3[N:19]([CH:26]4[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]4)[CH2:18][CH:17]=[C:11]4[NH:12][C:13](=[O:16])[C:14]=2[C:10]=34)=[C:5]([CH2:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:4]=[CH:3]1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate2×HCID 5360545Sodium2×HCID 90387726HCID 90387726, compound

Product 1

HCID 90388177HCID 90388177, compoundYield 84%

Conditions

Temperature
50 °C

Procedure

To a mixture of Example 6a (0.015 g, 0.044 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (0.017 g, 0.087 mmol) was added dichloroethane (1 mL) and acetic acid (0.03 mL, 0.524 mmol). The reaction mixture was heated at 50° C. for 2 hours, treated with sodium triacetoxyhydroborate (0.028 g, 0.131 mmol) and heated overnight at 50° C. Additional tert-butyl 4-oxopiperidine-1-carboxylate (0.017 g, 0.087 mmol) was added and the mixture was heated for 1 hour. Additional sodium triacetoxyhydroborate (0.028 g, 0.131 mmol) was added and the mixture was heated over a second night at 50° C. The reaction mixture was cooled to ambient temperature, partitioned between ethyl acetate and water, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography (silica gel, 0-6% methanol in dichloromethane) to give 0.0194 g (84%) of the title compound. 1H NMR (500 MHz, DMSO-d6) δ 10.71 (d, J=5.49 Hz, 1H), 7.69 (s, 1H), 7.64 (s, 1H), 7.13 (s, 1H), 6.79 (d, J=5.49 Hz, 1H), 4.40 (m, 2H), 4.11 (s, 3H), 3.87 (m, 2H), 3.73 (m, 1H), 3.63 (m, 1H), 3.19 (m, 1H), 2.91 (s, 3H), 2.66 (m, 2H), 1.67 (m, 1H), 1.58 (m, 1H), 1.45 (m, 2H), 1.38 (s, 9H), 1.23 (m, 1H). MS (ESI+) m/z 526.8 (M+H)+.

Workup

  1. temperatureheated overnight at 50° C
  2. temperaturethe mixture was heated for 1 hour
  3. temperaturethe mixture was heated over a second night at 50° C
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. custompartitioned between ethyl acetate and water
  6. washwashed with saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (silica gel, 0-6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-04274c1c57ee46908cd605776899298d
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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