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 500010Notes

Reaction equation

HRID 500010 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].Br[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.[Cl-].[NH4+]>O1CCCC1.C(OCC)C.C(OC)(C)(C)C>[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

9

Reactant 5

HCID 78391,2-DibromoethaneHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 117159911-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzeneHCID 11998864(2R,3S,5S)-5-Formyl-3-isopropyl-2-[4-methoxy-3-(3 methoxy-propoxy)-phenyl]pyrrolidine-1-carboxylic acid tert-butyl ester

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 ester

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A solution of 1.98 g of aldehyde 7 in 15 mL of tetrahydrofuran is cooled to 10° C. and is treated with the Grignard reagent prepared by treating 1.23 g of ((S)-2-bromomethyl-3-methylbutoxymethyl)-benzene with 0.12 g of magnesium in diethylether containing 0.043 g of 1,2-dibromoethane at 45° C. The reaction is stirred for 90 minutes at room temperature, then 20 mL of a 25% aqueous solution of ammonium chloride is added, followed by addition of 20 mL of tert-butylmethyl ether. The organic phase is separated and washed twice with 20 mL of water. The organic phase is concentrated in vacuum to give the crude alcohol 8 as an oil. Purification on silica-gel delivers e.g. 0.97 g of pure 8. A negative [a]d is found at c=1, CHCl3. M++H=628, M++H+Na=650.

Workup

  1. customprepared
  2. customThe organic phase is separated
  3. washwashed twice with 20 mL of water
  4. concentrationThe organic phase is concentrated in vacuum

Sources & evidence

ORD record
ord-a214f11502e444729b13dcd3ae735a95
Source dataset
uspto-grants-2010_08
Patent number
US07767831B2

Reaction notes

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