Triethylamine → HCID 23581851, compound

HRID 556226Notes

Reaction equation

HRID 556226 reaction equation
CCN(CC)CC.Br[CH2:9][CH2:10][OH:11].[OH:12][C@@H:13]1[C:29]([CH3:31])([CH3:30])[C:28](=[O:32])[C@H:27]([CH3:33])[C@@H:26]([OH:34])[C@@H:25]([CH3:35])[CH2:24][CH2:23][CH2:22][C@@H:21]2[C@@H:19]([NH:20]2)[CH2:18][C@@H:17](/[C:36](/[CH3:44])=[CH:37]/[C:38]2[N:39]=[C:40]([CH3:43])[S:41][CH:42]=2)[O:16][C:15](=[O:45])[CH2:14]1>C(#N)C>[OH:12][C@@H:13]1[C:29]([CH3:31])([CH3:30])[C:28](=[O:32])[C@H:27]([CH3:33])[C@@H:26]([OH:34])[C@@H:25]([CH3:35])[CH2:24][CH2:23][CH2:22][C@@H:21]2[C@@H:19]([N:20]2[CH2:9][CH2:10][OH:11])[CH2:18][C@@H:17](/[C:36](/[CH3:44])=[CH:37]/[C:38]2[N:39]=[C:40]([CH3:43])[S:41][CH:42]=2)[O:16][C:15](=[O:45])[CH2:14]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 108982-BromoethanolHCID 9913593HCID 9913593, compound

Product 1

HCID 23581851HCID 23581851, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
72.5 °C

Procedure

Et3N (4.95 mL, 35.52 mmol) and 2-bromoethanol (3.02 mL, 42.62 mmol) were added to (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12-tetramethyl-3-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4-oxa-17-azabicyclo[14.1.0]heptadecane-5,9-dione (3.50 g, 7.10 mmol) in acetonitrile (35 mL) and heated to 72.5° C. After 20 hr, the reaction mixture was cooled to room temperature, concentrated to dryness through rotary vacuum distillation. The crude was dissolved in ethyl acetate (50 mL) and mixed with deionized water (35 mL). The mixture was extracted with ethyl acetate (3×35 mL), dried over Na2SO4, filtered, concentrated, crystallized in acetonitrile (35 mL), washed with acetonitrile (2×5 mL), and dried in vacuum oven at 45.5° C. overnight to isolate (1S,3S,7S, 10R,11S,12S,16R)-7,11-dihydroxy-17-(2-hydroxyethyl)-8,8,10,12-tetramethyl-3-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4-oxa-17-azabicyclo[14.1.0]heptadecane-5,9-dione as a white crystalline powder (2.60 g, HPLC AP 97.1, 68.2% yield).

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. concentrationconcentrated to dryness through rotary vacuum distillation
  3. dissolutionThe crude was dissolved in ethyl acetate (50 mL)
  4. additionmixed with deionized water (35 mL)
  5. extractionThe mixture was extracted with ethyl acetate (3×35 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customcrystallized in acetonitrile (35 mL)
  10. washwashed with acetonitrile (2×5 mL)
  11. customdried in vacuum oven at 45.5° C. overnight

Sources & evidence

ORD record
ord-72d4d000810d4e7497d883dec79d9f7d
Source dataset
uspto-grants-2011_11
Patent number
USRE042930E1

Reaction notes

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