Triethylamine → Ethyl 2-(5-bromothiophen-2-yl)-2-(tert-butyldimethylsilyloxy)acetate

HRID 1484965Notes

Reaction equation

HRID 1484965 reaction equation
[Br:1][C:2]1[S:6][C:5]([CH:7]([OH:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][CH:3]=1.[CH3:14][C:15]([Si:18](Cl)([CH3:20])[CH3:19])([CH3:17])[CH3:16].C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl>[Br:1][C:2]1[S:6][C:5]([CH:7]([O:13][Si:18]([C:15]([CH3:17])([CH3:16])[CH3:14])([CH3:20])[CH3:19])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 12266238Ethyl 2-(5-bromothiophen-2-yl)-2-hydroxyacetate

Product 1

HCID 58169379Ethyl 2-(5-bromothiophen-2-yl)-2-(tert-butyldimethylsilyloxy)acetateYield 69.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl 2-(5-bromothiophen-2-yl)-2-hydroxyacetate (2.5 g, 9.43 mmol, 1.0 eq), DMAP (115 mg, 0.94 mmol, 0.1 eq) in dichloromethane (30 mL) was added TBDMSCl (2.85 g, 18.91 mmol, 2.0 eq) and triethylamine (5.0 mL, 35.97 mmol, 3.8 eq) at 0° C. After addition, the ice-water bath is removed and the mixture is allowed to reach room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed (brine), dried (Na2SO4), filtered and concentrated to give a residue, which was purified by silica gel column chromatography (PE:EA=50:1) to produce ethyl 2-(5-bromothiophen-2-yl)-2-(tert-butyldimethylsilyloxy)acetate (2.5 g, 69.9%). 1H NMR (400 MHz, DMSO-d6): δ 0.03 (s, 3H), 0.07 (s, 3H), 0.85 (s, 9H), 1.16 (t, J=7.0 Hz, 3H), 4.09-4.15 (m, 2H), 5.56 (d, J=0.8 Hz, 1H), 6.91-6.92 (m, 1H), 7.08 (d, J=4.0 Hz, 1H).

Workup

  1. additionAfter addition
  2. customthe ice-water bath is removed
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washwashed (brine)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a residue, which
  9. customwas purified by silica gel column chromatography (PE:EA=50:1)

Sources & evidence

ORD record
ord-b958a6d3c2e7480aa3274e7f31160233
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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