Oxygen → HCID 131737058, compound

HRID 59209Notes

Reaction equation

HRID 59209 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].O=O.Br[C:9]1[CH:14]=[CH:13][C:12]([Cl: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[CH:31]([O:65][CH2:66][C:67]2[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=2)[CH: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]([Cl: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 99964494-Bromo-1-chloro-2-(4-ethoxy-benzyl)-benzeneHCID 59226798HCID 59226798, compoundHCID 178418339Butyllithium

Product 1

HCID 131737058HCID 131737058, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-25 °C

Procedure

n-Butyl lithium (1.0 mL, 2.5 M/hexanes, 3.25 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-1-chloro-2-(4-ethoxy-benzyl)-benzene (815 mg, 3.25 equivalents) in anhydrous tetrahydrofuran (2.9 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 (l-1q) (600 mg) in anhydrous tetrahydrofuran (1.45 mL) was then added dropwise over 1.3 hours using a syringe pump and the resulting mixture was stirred at −78° C. for 1 hour before being allowed to warm to −25° C. over 14 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. Chromatography over silica gel using a gradient of 10 to 40% ethyl acetate in heptane gave the product as a mixture of isomers (280 mg, 38% yield). HRMS calculated for C59H61O10ClNa (M+Na+) 987.3845. found 987.3840.

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. customChromatography over silica gel using a gradient of 10 to 40% ethyl acetate in heptane gave the product
  15. additionas a mixture of isomers (280 mg, 38% yield)

Sources & evidence

ORD record
ord-c7b536dd3897498da70b78ad91c9ce86
Source dataset
uspto-grants-2016_09
Patent number
US09439902B2

Reaction notes

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