Ammonium Chloride → HCID 69655078, compound

HRID 1244003Notes

Reaction equation

HRID 1244003 reaction equation
[Cl-].[NH4+:2].C[Al](C)C.C[O:8][C:9]([CH:11]1[CH2:16][CH2:15][CH:14]([CH3:17])[N:13]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH:12]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=O>C1C=CC=CC=1.C1(C)C=CC=CC=1>[CH2:21]([O:20][C:18]([N:13]1[C@H:14]([CH3:17])[CH2:15][CH2:16][C@@H:11]([C:9](=[O:8])[NH2:2])[C@@H:12]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 16682925TrimethylaluminumHCID 69654922HCID 69654922, compound

Product 1

HCID 69655078HCID 69655078, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

(A mixture of two diastereomers and their enantiomers.). To ammonium chloride (1.18 g, 22.1 mmol) in 20 mL of benzene at 0° C. was added trimethylaluminum (22.1 mmol, 11.0 mL of a 2.0 M solution in toluene) The resultant mixture was stirred for 30 minutes at 0° C., and warmed to room temperature for an additional 30 minutes. To the mixture was then added 6-Methyl-2-phenyl-piperidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester as a solution in 20 mL of benzene, and the resultant mixture was heated to reflux for 6 hours. The reaction was then cooled to 0° C. and quenched carefully with 10 mL of 1 M HCl. The mixture was stirred for 30 minutes, filtered through celite, and the filter pad was rinsed with CH2Cl2. The filtrate was concentrated and the residue was dissolved in EtOAc, washed with saturated NaHCO3, dried over MgSO4 and concentrated. Silica gel chromatography (CHCl3 to eluted nonpolar material followed by 95:5 CHCl3/MeOH to elute the product) gave 560 mg (36%) of a mixture of the title compounds as a white foam. 1H NMR (400 MHz, CDCl3) δ 7.10–7.42 (comp, 20H, both diastereomers), 5.99 (d, J=5.1 Hz, 1H), 5.68–5.90 (br, 2H, both diastereomers), 5.67 (d, J=4.3 Hz, 1H), 5.00–5.26 (comp, 4H, both diastereomers), 4.53 (m, 1H), 4.17 (br, 1H), 3.15 (m, 1H), 2.75 (m, 1H), 2.28 (app dq, J=4.1, 13.2 Hz, 1H), 1.9–2.08 (m, 2H), 1.50–1.90 (comp, 5H), 1.34 (d, J=6.6 Hz, 3H), 0.68 (d, J=7.1 Hz, 3H); 13C NMR (100 MHz) δ 174.2, 128.6, 128.4, 128.3, 128.2, 128.1, 127.8, 127.6, 127.2, 127.1, 126.7, 67.6, 67.1, 56.9, 52.8, 47.4, 46.6, 30.2, 25.5, 22.3, 19.8, 16.3; Mass spectrum m/e calcd. for M+H=353.2. Found 353.0, 309.1, 219.0 (base).

Workup

  1. addition(A mixture of two diastereomers and their enantiomers
  2. temperaturewarmed to room temperature for an additional 30 minutes
  3. temperatureto reflux for 6 hours
  4. temperatureThe reaction was then cooled to 0° C.
  5. customquenched carefully with 10 mL of 1 M HCl
  6. stirringThe mixture was stirred for 30 minutes
  7. filtrationfiltered through celite
  8. washthe filter pad was rinsed with CH2Cl2
  9. concentrationThe filtrate was concentrated
  10. dissolutionthe residue was dissolved in EtOAc
  11. washwashed with saturated NaHCO3
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated
  14. washSilica gel chromatography (CHCl3 to eluted nonpolar material
  15. washto elute the product)

Sources & evidence

ORD record
ord-d6f240ba443d4bfc87c9ff7368194043
Source dataset
uspto-grants-2006_10
Patent number
US07119207B2

Reaction notes

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