Oxygen → HCID 86639769, compound

HRID 659898Notes

Reaction equation

HRID 659898 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].O=O.Br[C:9]1[CH:10]=[CH:11][C:12]([F:28])=[C:13]([CH:27]=1)[CH2:14][C:15]1[CH:26]=[CH:25][C:18]([O:19][CH:20]2[CH2:24][CH2:23][O:22][CH2:21]2)=[CH:17][CH:16]=1.CON(C)[C:32](=[O:84])[C@H:33]([O:76]CC1C=CC=CC=1)[C@@H:34]([O:68][CH2:69][C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=1)[C@H:35]([O:60][CH2:61][C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)[C:36]([OH:59])([CH2:48][O:49][CH2:50][C:51]1[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=1)[CH2:37][O:38][CH2:39][C:40]1[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=1.[Al].O1C[CH2:90][CH2:89][CH2:88]1>C(OCC)C>[CH2:1]([O:76][CH:33]1[C@@H:34]([O:68][CH2:69][C:70]2[CH:71]=[CH:72][CH:73]=[CH:74][CH:75]=2)[C@H:35]([O:60][CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[C:36]([CH2:48][O:49][CH2:50][C:51]2[CH:52]=[CH:53][C:54]([O:57][CH3:58])=[CH:55][CH:56]=2)([CH2:37][O:38][CH2:39][C:40]2[CH:41]=[CH:42][C:43]([O:46][CH3:47])=[CH:44][CH:45]=2)[O:59][C:32]1([C:9]1[CH:10]=[CH:11][C:12]([F:28])=[C:13]([CH2:14][C:15]2[CH:26]=[CH:25][C:18]([O:19][CH:20]3[CH2:24][CH2:23][O:22][CH2:21]3)=[CH:17][CH:16]=2)[CH:27]=1)[OH:84])[C:2]1[CH:90]=[CH:89][CH:88]=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 977OxygenHCID 8028Tetrahydrofuran2×HCID 5359268AluminumHCID 59226798(2R,3S,4S)-2,3,4-tris-benzyloxy-5-hydroxy-6-(4-methoxy-benzyloxy)-5-(4-methoxy-benzyloxymethyl)-hexanoic acid methoxy-methyl-amideHCID 66615927HCID 66615927, compoundHCID 178418339Butyllithium

Product 1

HCID 86639769HCID 86639769, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
10 °C

Procedure

n-Butyl lithium (1.0 mL, 2.5 M/hexanes, 3.0 equivalents) was added dropwise (1 drop every 5 seconds) to an oxygen degassed solution of 3-[4-(5-bromo-2-fluoro-benzyl)-phenoxy]-tetrahydro-furan (878 mg, 2.50 mmol) in anhydrous tetrahydrofuran (3.0 mL) at −78° C. and the resulting solution was stirred at this temperature for 1 hour. A solution of (2R,3S,4S)-2,3,4-tris-benzyloxy-5-hydroxy-6-(4-methoxy-benzyloxy)-5-(4-methoxy-benzyloxymethyl)-hexanoic acid methoxy-methyl-amide I-1g (650 mg, 0.833 mmol) in anhydrous tetrahydrofuran (1.5 mL) was then added dropwise very slowly (0.9 mL/hour) and the resulting mixture was stirred at −78° C. for an additional hour before warming to 10° C. over 12 hours (put in a deep Dewar covered with aluminum foil to maintain cold temperature). The reaction was diluted with diethyl ether and quenched by the dropwise addition of aqueous 1N hydrochloric acid solution. The resulting biphasic mixture was stirred at room temperature for 15 minutes. The organic phase was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (eluting with a gradient of 10 to 40% ethyl acetate in heptane) to afford the product as a mixture of isomers (287 mg, 34% yield)

Workup

  1. stirringthe resulting mixture was stirred at −78° C. for an additional hour
  2. temperatureto maintain cold temperature)
  3. customquenched by the dropwise addition of aqueous 1N hydrochloric acid solution
  4. stirringThe resulting biphasic mixture was stirred at room temperature for 15 minutes
  5. customThe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude residue was purified by flash chromatography over silica gel (
  11. washeluting with a gradient of 10 to 40% ethyl acetate in heptane)
  12. customto afford the product
  13. additionas a mixture of isomers (287 mg, 34% yield)

Sources & evidence

ORD record
ord-1acf6ca886c5470694a526243e84d0e9
Source dataset
uspto-grants-2011_12
Patent number
US08080580B2

Reaction notes

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