Cesium carbonate → Tert-butyl 1-(isopropoxycarbonyl)-4-oxo-3-o-tolylpentylcarbamate

HRID 706382Notes

Reaction equation

HRID 706382 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:16]OS(C)(=O)=O)[C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]1([CH3:32])[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][C:29](=[O:31])[CH3:30].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.CS(C)=O>[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:16][CH:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[CH3:32])[C:29](=[O:31])[CH3:30])[C:10]([O:12][CH:13]([CH3:14])[CH3:15])=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27341091-(2-Methylphenyl)propan-2-oneHCID 89815000isopropyl N-(tert-butoxycarbonyl)-O-(methylsulfonyl)serinate

Product 1

HCID 89814785Tert-butyl 1-(isopropoxycarbonyl)-4-oxo-3-o-tolylpentylcarbamateYield 65.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2 (181.2 g, 0.557 mol) in THF (1 L) was added TEA (84.6 g, 0.836 mol) in portions at 15-20° C. The mixture was stirred for 30 h. After the reaction was complete, the solution was concentrated to give crude 7. To a solution of 35 (82.5 g, 0.557 mol) and Cs2CO3 (91 g, 0.279 mol) in DMSO (1 L) was added slowly crude 7 in DMSO (500 mL) over 30 min at 15-20° C. The mixture was stirred for 1 h. After the reaction was complete, the mixture was partitioned with water and MTBE (5 L), and extracted with MTBE twice. The combined organic layer was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE) to give 36 (138 g, 65% yield).

Workup

  1. concentrationthe solution was concentrated
  2. customto give crude 7
  3. stirringThe mixture was stirred for 1 h
  4. customthe mixture was partitioned with water and MTBE (5 L)
  5. extractionextracted with MTBE twice
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude residual was further purified by flash chromatography on silica gel (5-10% EtOAc/PE)

Sources & evidence

ORD record
ord-1e1c02338f0f4433b4880d4b3b6b275f
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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