Methanol → HCID 66704846, compound

HRID 2108806Notes

Reaction equation

HRID 2108806 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[C@@H:10]([CH2:14]O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:36].CO>CN(C)C(=O)C.ClCCl.C(OCC)(=O)C>[Br:36][CH2:14][C@@H:10]1[C@@H:11]([OH:13])[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]1

Participants

8

Reactant 4

HCID 887MethanolHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 11252928HCID 11252928, compound

Product 1

HCID 66704846HCID 66704846, compoundYield 67.5%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

(3R,4R)-(1-tert-Butoxycarbonyl-4-hydroxypyrrolidin-3-yl)methanol (3.64 g) and triphenylphosphine (4.41 g) were dissolved in N,N-dimethylacetamide (84 mL). While the solution was chilled in an ice water bath, carbon tetrabromide (5.57 g) in dichloromethane (16 mL) was added dropwise. The mixture was stirred at room temperature for 13 hours, followed by addition of methanol (8 mL) and concentration under reduced pressure. The resulting residue was dissolved in ethyl acetate (300 mL), washed sequentially with water (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: ethyl acetate: hexane=2:1) to give (3S,4R)-3-bromomethyl-1-tert-butoxycarbonyl-4-hydroxypyrrolidine as a milky white syrup (3.17 g).

Workup

  1. temperatureWhile the solution was chilled in an ice water bath
  2. washwashed sequentially with water (100 mL) and saturated brine (100 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (eluant: ethyl acetate: hexane=2:1)

Sources & evidence

ORD record
ord-b3c9ddad829243eba85a434544806fb4
Source dataset
uspto-grants-2009_04
Patent number
US07514451B2

Reaction notes

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