1,2-Dibromoethane → (2R,3S,5S)-5-((1S,3S)-3-Benzyloxymethyl-1-hydroxy-4-methyl-pentyl)-3-isopropyl-2-[4-methoxy-3-(3 methoxy-propoxy)-phenyl]pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 500011Notes

Reaction equation

HRID 500011 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH:13]=[O:14])[CH2:11][C@@H:10]([CH:15]([CH3:17])[CH3:16])[C@@H:9]1[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:33][C@@H:34]([CH:44]([CH3:46])[CH3:45])[CH2:35][O:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[Mg].BrCCBr>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C@H:12]([C@@H:13]([OH:14])[CH2:33][C@H:34]([CH2:35][O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:44]([CH3:45])[CH3:46])[CH2:11][C@@H:10]([CH:15]([CH3:17])[CH3:16])[C@@H:9]1[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 78391,2-DibromoethaneHCID 5462224Magnesium2×HCID 11998864(2R,3S,5S)-5-Formyl-3-isopropyl-2-[4-methoxy-3-(3 methoxy-propoxy)-phenyl]pyrrolidine-1-carboxylic acid tert-butyl esterHCID 59336256((S)-2-chloromethyl-3-methyl-butoxymethyl)-benzene

Product 1

HCID 67304985(2R,3S,5S)-5-((1S,3S)-3-Benzyloxymethyl-1-hydroxy-4-methyl-pentyl)-3-isopropyl-2-[4-methoxy-3-(3 methoxy-propoxy)-phenyl]pyrrolidine-1-carboxylic acid tert-butyl esterYield 109.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Alternatively, A solution of 27 g of aldehyde 7 in 30 mL of tetrahydrofuran is added to a room-temperature solution of the Grignard reagent prepared by refluxing 20 g of ((S)-2-chloromethyl-3-methyl-butoxymethyl)-benzene with 3.2 g of magnesium in 120 mL of tetrahydrofuran containing 1.3 g of 1,2-dibromoethane for 4 h. The reaction is stirred for 1 h at room temperature, then 100 mL of 2 N sulfuric add is added. The mixture is stirred until the excess magnesium has dissolved, then the phases are separated and the organic phase washed with 50 mL of 12% sodium chloride solution. The organic phase is concentrated in vacuum to give e.g. 42.6 g of the crude alcohol 8 as an oil.

Workup

  1. customprepared
  2. addition100 mL of 2 N sulfuric add
  3. additionis added
  4. dissolutionhas dissolved
  5. customthe phases are separated
  6. washthe organic phase washed with 50 mL of 12% sodium chloride solution
  7. concentrationThe organic phase is concentrated in vacuum

Sources & evidence

ORD record
ord-c7d259f314fc4393b1a2185a4dd62ba0
Source dataset
uspto-grants-2010_08
Patent number
US07767831B2

Reaction notes

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