Triethylamine → (S,S)-1-{5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-2-hydroxy-ethanone

HRID 545606Notes

Reaction equation

HRID 545606 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[O:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=1.Cl.[CH:20]12[CH2:26][CH:23]([NH:24][CH2:25]1)[CH2:22][N:21]2[C:27](=[O:30])[CH2:28][OH:29].CCN(CC)CC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.CN1CCCC1=O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[O:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][N:24]2[CH2:25][C@@H:20]3[CH2:26][C@H:23]2[CH2:22][N:21]3[C:27](=[O:30])[CH2:28][OH:29])=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 326778754-(Benzothiazol-2-yloxy)-benzaldehydeHCID 672076771-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-2-hydroxy-ethanone hydrochloride

Product 1

HCID 67206856(S,S)-1-{5-[4-(Benzothiazol-2-yloxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-yl}-2-hydroxy-ethanoneYield 91.3%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 4-(benzothiazol-2-yloxy)-benzaldehyde (67 g, 0.26 mol), 1-(2,5-diaza-bicyclo[2.2.1]hept-2-yl)-2-hydroxy-ethanone hydrochloride (40.61 g, 0.26 mol), Et3N (183 mL, 1.31 mol), and N-methylpyrrolidinone (150 mL) in dichloroethane (750 mL) was stirred at rt for 1 h. Sodium triacetoxyborohydride (66.63 g, 0.314 mol) was then added in four equal portions over a 4 h period. After stirring overnight, the mixture was quenched with 3 N HCl(aq) (250 mL) and then 6 N HCl(aq) (3×50 mL) to a final pH of 0.54. The layers were separated and the organic was extracted again with 3 N HCl(aq) (250 mL). The combined aqueous layers were basified with Na2CO3 (50 g) and then 50% NaOH(aq) (130 mL) to a final pH of 13.2. After stirring for 1 h, isopropyl acetate (200 mL) was added and the mixture was stirred for 20 min. After separation of layers, the aqueous was extracted with additional isopropyl acetate (2×200 mL) and the organic layers were combined with an interstitial oil and concentrated. The resulting brown oil was purified by flash chromatography (0-5% MeOH in CH2Cl2) to provide the product as a clear oil (93.84 g, 91%).

Workup

  1. stirringAfter stirring overnight
  2. customthe mixture was quenched with 3 N HCl(aq) (250 mL)
  3. customThe layers were separated
  4. extractionthe organic was extracted again with 3 N HCl(aq) (250 mL)
  5. stirringAfter stirring for 1 h
  6. additionisopropyl acetate (200 mL) was added
  7. stirringthe mixture was stirred for 20 min
  8. customAfter separation of layers
  9. extractionthe aqueous was extracted with additional isopropyl acetate (2×200 mL)
  10. concentrationconcentrated
  11. customThe resulting brown oil was purified by flash chromatography (0-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-a7e2d9b438544c05881ac07851d3ebb0
Source dataset
uspto-grants-2011_05
Patent number
US07935725B2

Reaction notes

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