Oxygen → HCID 59226839, compound

HRID 659893Notes

Reaction equation

HRID 659893 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].O=O.Br[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=2)[CH:10]=1.CON(C)[C:29](=[O:81])[C@H:30]([O:73]CC1C=CC=CC=1)[C@@H:31]([O:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)[C@H:32]([O:57][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[C:33]([OH:56])([CH2:45][O:46][CH2:47][C:48]1[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[CH:50][CH:49]=1)[CH2:34][O:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=1.[Al].O1C[CH2:87][CH2:86][CH2:85]1>C(OCC)C>[CH2:1]([O:73][CH:30]1[C@@H:31]([O:65][CH2:66][C:67]2[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=2)[C@H:32]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:33]([CH2:45][O:46][CH2:47][C:48]2[CH:49]=[CH:50][C:51]([O:54][CH3:55])=[CH:52][CH:53]=2)([CH2:34][O:35][CH2:36][C:37]2[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=2)[O:56][C:29]1([C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=2)[CH:10]=1)[OH:81])[C:2]1[CH:87]=[CH:86][CH:85]=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 977OxygenHCID 8028Tetrahydrofuran2×HCID 5359268AluminumHCID 46205791HCID 46205791, compoundHCID 59226798(2R,3S,4S)-2,3,4-tris-benzyloxy-5-hydroxy-6-(4-methoxy-benzyloxy)-5-(4-methoxy-benzyloxymethyl)-hexanoic acid methoxy-methyl-amideHCID 178418339Butyllithium

Product 1

HCID 59226839HCID 59226839, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

n-Butyl lithium (0.312 mL, 2.5 M/hexanes, 3.05 equivalents) was added dropwise (1 drop every 5 seconds) to an oxygen degassed solution (placed in a pre dried Biotage™ microwave vial 10-20 mL sealed with its cap and placed under a positive stream of nitrogen gas) of 4-bromo-2-(4-ethoxy-benzyl)-1-methyl-benzene (238 mg, 3.05 equivalents) in anhydrous tetrahydrofuran (0.9 mL) at −78° C. and the resulting solution was stirred at this temperature for an additional 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) (200 mg) in anhydrous tetrahydrofuran (0.6 mL) was then added dropwise over 1.5 hours using a syringe pump and the resulting mixture was stirred at −78° C. for 1 hour before being allowed to warm to room temperature over 16 hours (put in a deep Dewar covered with aluminum foil to maintain cold temperature; size of Dewar: external diameter 10 cm, internal diameter 8 cm, height 9 cm). Diethyl ether was added and the reaction was quenched by dropwise addition of aqueous 1M 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. The crude material was chromatographed using the Biotage™ automated chromatography unit (two stacked 10 g silica gel columns; eluting with a gradient of 0 to 60% ethyl acetate in heptane) to give the product as a mixture of isomers (136 mg, 56% yield). MS (LCMS) 968 (M+Na+; positive mode).

Workup

  1. customdried Biotage™ microwave vial 10-20 mL
  2. customsealed with its
  3. customcap
  4. customat −78° C.
  5. stirringthe resulting mixture was stirred at −78° C. for 1 hour
  6. temperatureto maintain cold temperature
  7. customthe reaction was quenched by dropwise addition of aqueous 1M hydrochloric acid solution
  8. stirringThe resulting biphasic mixture was stirred at room temperature for 15 minutes
  9. customThe organic phase was separated
  10. washwashed with brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude material was chromatographed
  15. washeluting with a gradient of 0 to 60% ethyl acetate in heptane)
  16. customto give the product
  17. additionas a mixture of isomers (136 mg, 56% yield)

Sources & evidence

ORD record
ord-8877319e7cb94a6fb99b5a1c909b4994
Source dataset
uspto-grants-2011_12
Patent number
US08080580B2

Reaction notes

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