L-Threonine → HCID 54359123, compound

HRID 1281408Notes

Reaction equation

HRID 1281408 reaction equation
[NH:1]1[CH:5]=[N:4][N:3]=[N:2]1.[H-].[Na+].[CH2:8]([NH:20][C:21](=[O:41])[C:22]1[CH:27]=[C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=2)[C:25]([O:36][CH2:37][CH2:38]Br)=[C:24]([Br:40])[CH:23]=1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].N[C@H](C(O)=O)[C@@H](C)O>C1COCC1.CCOC(C)=O.CS(C)=O>[CH2:8]([NH:20][C:21]([C:22]1[CH:27]=[C:26]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=2)[C:25]([O:36][CH2:37][CH2:38][N:1]2[CH:5]=[N:4][N:3]=[N:2]2)=[C:24]([Br:40])[CH:23]=1)=[O:41])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]

Participants

8

Reactant 4

HCID 6288L-ThreonineHCID 24758Sodium hydrideHCID 22237523HCID 22237523, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 54359123HCID 54359123, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 1H-tetrazole (28 mg, 0.4 mmol) in 1 mL anhydrous THF at 0° C. was added NaH (10 mg, 0.421 mmol). The reaction mixture was stirred for 10 min at 0° C. after which point a solution of N-dodecyl-3-bromo-4-(2-bromoethoxy)-5-(3-methoxyphenyl)benzamide (160 mg, 0.276 mmol) in 2.5 mL anhydrous THF was added. The reaction mixture was stirred at 0° C. for 10 min then allowed to warm up to room temperature for one-half hour. Then 700 μL of DMSO was added and the reaction was then heated at 65° C. overnight. Thr reaction was quenched and diluted with water and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4 and the solvent removed in vacuo to give a brown-yellow oil. The crude material was subjected to flash column chromatography (25% EtOAc:75% Hexanes to 40% EtOAc:60% Hexanes to 50% EtOAc:50% Hexanes) to yield 40 mg, 25% of a white solid. mp 100-1° C. ; 1H NMR (DMSO-d6) δ 0.88 (t, J=6.80 Hz, 3H); 1.25-1.37 (m, 18H); 1.60 (quintet, J=7.14 Hz, 2H); 3.43 (q, J=7.14 Hz, 2H); 3.84 (s, 3H); 3.96 (t, J=4.86 Hz, 2H); 4.57 (t, J=4.86 Hz, 2H); 6.01 (t, J=5.00 Hz, 1H); 6.93-6.95 (m, 3H); 7.27-7.32 (m, 1H); 7.64 (d, J=2.20 Hz, 1H); 7.94 (d, J=1.98 Hz, 1H); 8.68 (s, 1H); IR 3330, 2900, 2840, 1625, 1600, 1520, 1460, 1310, 1300, 1235, 1175, and 1030 cm−1; mass spectrum [(+)ESI] m/z 586/588 [M+H]+; Anal Calcd. For C29H40BrN5O3: C, 59.38; H, 6.87; N, 11.94; Found: C, 59.46; H, 6.68; N, 11.77.

Workup

  1. additionwas added
  2. temperatureto warm up to room temperature for one-half hour
  3. temperaturethe reaction was then heated at 65° C. overnight
  4. customwas quenched
  5. additiondiluted with water
  6. extractionextracted with EtOAc (3×)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. customthe solvent removed in vacuo
  9. customto give a brown-yellow oil

Sources & evidence

ORD record
ord-16e29ae23fdb42c488f31058bbd862fc
Source dataset
uspto-grants-2002_09
Patent number
US06451827B2

Reaction notes

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