Bromoacetyl bromide → HCID 66654190, compound

HRID 2036245Notes

Reaction equation

HRID 2036245 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:25])[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1[CH:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][NH:16]1)[CH3:3].C(N(C(C)C)C(C)C)C.[Br:35][CH2:36][C:37](Br)=[O:38]>C(Cl)Cl>[CH2:2]([O:4][C:5](=[O:25])[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1[CH:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][N:16]1[C:37](=[O:38])[CH2:36][Br:35])[CH3:3]

Participants

5

Reactant 3

HCID 61147Bromoacetyl bromideHCID 81531DiisopropylethylamineHCID 66654555HCID 66654555, compound

Product 1

HCID 66654190HCID 66654190, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled solution under N2 of (±)-[4-fluoro-2-(1,2,3,4-tetrahydro-isoquinolin-1-yl)-phenoxy]-acetic acid ethyl ester hydrochloride (2.0 g, 5.2 mmol, 1.0 eq.) in DCM (13 mL), N-ethyldiisopropylamine (2.7 mL, 15.6 mmol, 3.0 eq.) was added. A solution of bromoacetyl bromide (0.5 mL, 5.7 mmol, 1.1 eq.) in DCM (5 mL) was added dropwise. The cooling bath was removed and the brown solution stirred at r.t. for 2 hours. The solution was diluted with AcOEt (170 mL), washed with sat. aq. NaHCO3 soln. (1×90 mL), with sat. aq. NaCl soln. (1×90 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash master (column: 100 g, flow: 35 mL/min, heptane to heptane+AcOEt) to yield the title compound as a brown oil.

Workup

  1. additionwas added
  2. customThe cooling bath was removed
  3. additionThe solution was diluted with AcOEt (170 mL)
  4. washwashed with sat. aq. NaHCO3 soln
  5. dry with material(1×90 mL), dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash master (column: 100 g, flow: 35 mL/min, heptane to heptane+AcOEt)

Sources & evidence

ORD record
ord-11026265cdff4c1b97852bd69dc7a9de
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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