Imidazole → 2-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethane

HRID 1985983Notes

Reaction equation

HRID 1985983 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([OH:18])[CH2:16][Br:17])=[CH:11][C:10]=1[NH:19][CH:20]=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:22](Cl)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23].N1C=CN=C1>CN(C)C=O.CN(C)C1C=CN=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH2:16][Br:17])=[CH:11][C:10]=1[NH:19][CH:20]=[O:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 21880606Benzenesulfonyl chloride, 4-(acetylamino)-3-methyl-

Product 1

HCID 574610672-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethaneYield 104%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[2-benzyloxy-5-(2-bromo-1-hydroxyethyl)phenyl]formamide (Organic Process Research and Development 1998, 2, 96-99) (4.12 g, 11.8 mmol) in N,N-dimethylformamide (25 mL) at RT under N2 was added tert-butyldimethylsilyl chloride (3.50 g, 23.2 mmol), imidazole (1.90 g, 27.9 mmol) and 4-(dimethylamino)pyridine (40 mg, 330 □mol). The resulting solution was stirred at RT overnight, the solvent was removed and the product taken up in ethyl acetate (70 mL). The organics were washed with water (100 mL), and the aqueous extracted with ethyl acetate (20 mlmL The combined organics were washed with hydrochloric acid (2M, 50 ml), brine (100 mL) and dried (MgSO4). The crude material was purified by chromatography (5-25% ethyl acetate in pentane) to yield a colourless oil (5.7 g). 1HNMR (CDCl3, 400 MHz) δ: −0.08 to −0.05 (3H, m), 0.09-0.11 (3H, s), 0.89-0.90 (9H, m), 3.38-3.55 (2H, m), 3.78-3.84 (1H, m), 5.06-5.11 (2H, m), 6.90-6.97 (1H, m), 7.03-7.12 (1H, m), 7.24 (m), 7.36-7.43 (5H, m), 7.67-7.78 (m), 7.88 (d), 8.74 (d); LRMS APCI m/z 464/466 [M+H]+

Workup

  1. customthe solvent was removed
  2. washThe organics were washed with water (100 mL)
  3. extractionthe aqueous extracted with ethyl acetate (20 mlmL The combined
  4. washorganics were washed with hydrochloric acid (2M, 50 ml), brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. customThe crude material was purified by chromatography (5-25% ethyl acetate in pentane)

Sources & evidence

ORD record
ord-9a144f756ed047f295d38a2aa8a6bfb1
Source dataset
uspto-grants-2009_06
Patent number
US07547731B2

Reaction notes

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