Dichloromethane → (S)-methyl 3-((2-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-5-(trifluoromethyl)benzoate

HRID 473106Notes

Reaction equation

HRID 473106 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][C@H:7]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6]2.CC1(C)COB([C:30]2[CH:31]=[C:32]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=2)[C:33]([O:35][CH3:36])=[O:34])OC1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>C1COCC1>[CH2:15]([O:14][C:13]([NH:12][C@@H:7]1[CH2:6][C:5]2[C:9](=[CH:10][CH:11]=[C:3]([CH2:2][C:30]3[CH:31]=[C:32]([CH:37]=[C:38]([C:40]([F:41])([F:43])[F:42])[CH:39]=3)[C:33]([O:35][CH3:36])=[O:34])[CH:4]=2)[CH2:8]1)=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 66734229Methyl 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5-(trifluoromethyl)benzoateHCID 70223052(S)-benzyl 5-(chloromethyl)-2,3-dihydro-1H-inden-2-ylcarbamate

Product 1

HCID 70223635(S)-methyl 3-((2-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-5-(trifluoromethyl)benzoateYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To (S)-benzyl 5-(chloromethyl)-2,3-dihydro-1H-inden-2-ylcarbamate (7.09 mmol, 2.24 g) in THF (44.9 mL) was added methyl 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5-(trifluoromethyl)benzoate (7.09 mmol, 2.242 g), Bromo(N-succinimidyl)bis-(triphenylphosphine)palladium(II) (0.355 mmol, 0.287 g) and sodium carbonate (45.0 mmol, 22.5 mL). The reaction was heated to 80° C. for 4 hrs. DCM was added before washing with water (×1) followed by brine (×1). The organics were dried over MgSO4 before removing the solvent in vacuo. The crude material was purified by silica chromatography (5:1>2:1, hep EtOAc). The solvent was removed to give the title compound as a white solid (2.6 g, 76%). MS (ESI): m/z [M+H]+ 484.2

Workup

  1. washbefore washing with water (×1)
  2. dry with materialThe organics were dried over MgSO4
  3. custombefore removing the solvent in vacuo
  4. customThe crude material was purified by silica chromatography (5:1>2:1, hep EtOAc)
  5. customThe solvent was removed

Sources & evidence

ORD record
ord-f8b77f502f2c45e6b8624fe38b29ec94
Source dataset
uspto-grants-2014_01
Patent number
US08633237B2

Reaction notes

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