Tetrahydrofuran → (S)-1-(1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylurea

HRID 416392Notes

Reaction equation

HRID 416392 reaction equation
[CH:1]1[C:6]([N+:7]([O-])=O)=[CH:5][CH:4]=[C:3]([Cl-]C([O-])=O)C=1.Cl.[Cl:15][C:16]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:17]=1[CH2:18][NH2:19].[CH3:25]CN(C(C)C)C(C)C.[Si:34]([O:41]C[C@@H](NC)CC=C)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35].C1C[O:52][CH2:51]C1>>[Si:34]([O:41][CH2:1][C@@H:6]([N:7]([CH3:25])[C:51]([NH:19][CH2:18][C:17]1[CH:20]=[CH:21][CH:22]=[C:23]([F:24])[C:16]=1[Cl:15])=[O:52])[CH2:5][CH:4]=[CH2:3])([C:37]([CH3:38])([CH3:39])[CH3:40])([CH3:35])[CH3:36]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 81531DiisopropylethylamineHCID 57947450(S)-1-(tert-butyldimethylsilyloxy)-N-methylpent-4-en-2-amineHCID 66622557(2-Chloro-3-fluorophenyl)methanamine hydrochloride

Product 1

HCID 57947454(S)-1-(1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylureaYield 76%

Procedure

To a solution of 4-nitrophenylchloroformate (7.69 g, 38.3 mmol) in THF (20 mL) was added a solution of 2-chloro-3-fluorobenzylamine hydrochloride (6.09 g, 38.3 mmol) and DIEA (7.9 mL, 47.9 mmol) in THF (20 mL). The resulting solution was stirred at RT for 20 min. The reaction mixture was added into a solution of (S)-1-(tert-butyldimethylsilyloxy)-N-methylpent-4-en-2-amine (31.9 mmol) in THF (100 mL). The resulting solution was stirred at RT overnight. The solvent was removed and the resulting residue was re-dissolved in EtOAc (500 mL). The organic mixture was washed with NaOH (1 N, 100 mL×3), HCl (0.5 N, 100 mL), saturated NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel column using a mixture of DCM and MeOH to give (S)-1-(1-(tert-butyldimethylsilyloxy)pent-4-en-2-yl)-3-(2-chloro-3-fluorobenzyl)-1-methylurea (10.08 g, 76%) as a white solid. LRMS (M+H+) m/z 415.2.

Workup

  1. stirringThe resulting solution was stirred at RT overnight
  2. customThe solvent was removed
  3. dissolutionthe resulting residue was re-dissolved in EtOAc (500 mL)
  4. washThe organic mixture was washed with NaOH (1 N, 100 mL×3), HCl (0.5 N, 100 mL), saturated NaHCO3, and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on silica gel column
  9. additiona mixture of DCM and MeOH

Sources & evidence

ORD record
ord-0501da99d5af407c8fd10ff8e6435f10
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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