Ammonium Chloride → HCID 68768691, compound

HRID 1170411Notes

Reaction equation

HRID 1170411 reaction equation
[CH:1]([C@H:4]1[C:9]([O:10][CH3:11])=[N:8][CH:7]([CH3:12])[C:6]([O:13][CH3:14])=[N:5]1)([CH3:3])[CH3:2].C([Li])CCC.I[CH2:21][CH2:22][C:23]1[CH:24]=[CH:25][C:26]2[O:30][C:29]([CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])=[N:28][C:27]=2[CH:36]=1.[Cl-].[NH4+]>C1COCC1.CCCCCC.CCOC(C)=O>[CH:1]([C@H:4]1[C:9]([O:10][CH3:11])=[N:8][C@@:7]([CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]3[O:30][C:29]([CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])=[N:28][C:27]=3[CH:36]=2)([CH3:12])[C:6]([O:13][CH3:14])=[N:5]1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 13049214HCID 13049214, compoundHCID 687659935-(2-Iodo-ethyl)-2-pentyl-benzoxazoleHCID 178418339Butyllithium

Product 1

HCID 68768691HCID 68768691, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-65 °C

Procedure

Under an argon atmosphere, a −70° C. solution of (S)-2-Isopropyl-3,6-dimethoxy-5-methyl-2,5-dihydro-pyrazine (652.5 μl, 3.291 mmol) in dry THF (7 ml) was treated with a solution of n-butyl lithium in n-hexane (2.1 ml of a 1.6M solution, 3.29 mmol). After stirring for 10 minutes a solution of 5-(2-iodo-ethyl)-2-pentyl-benzoxazole (753 mg, 2.19 mmol) in dry THF (5 ml) was added and the reaction mixture was stirred for 90 minutes at −65° C. followed by 2 hours at 0-5° C. The reaction was distributed between AcOEt and saturated aqueous ammonium chloride. The organic layer dried over MgSO4 and concentrated in vacuum. Silica-gel flash chromatography (pentane/diethyl ether 4/1) provided the crude 5-[2-((2R,5S)-5-Isopropyl-3,6-dimethoxy-2-methyl-2,5-dihydro-pyrazin-2-yl)-ethyl]-2-pentyl-benzoxazole. The crude product was dissolved in acetonitrile (21 ml) and treated with water (21 ml) and trifluoroacetic acid (450 μl) and stirred for 3 days at RT. The solvents were removed in vacuum and the title compound was obtained after reversed phase chromatography (Waters, C-18, eluent: gradient of water/acetonitrile containing 0.1% trifluoroacetic acid) as an amorphous solid. 1H-NMR (CDCl3) δ: 8.50 (s; 1H), 6.98 (s; 1H); 8.86/6.83 (2 broad singlets; 2H), 3.71 (s; 3H), 2.75-2.35 (m; 4H), 2.20 (broad s; 2H), 1.70 (broad s; 2H), 1.61 (s; 3H), 1.40-1.20 (m; 4H), 0.90 (m; 3H).

Workup

  1. additionwas added
  2. waitfollowed by 2 hours at 0-5° C
  3. dry with materialThe organic layer dried over MgSO4
  4. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-997f3ca8cda649b6834bc9ee8d8dcfbc
Source dataset
uspto-grants-2010_11
Patent number
US07825260B2

Reaction notes

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