Cesium carbonate → Isopropyl 2-((tert-butoxycarbonyl)amino)-5-oxo-4-(2,3,5-trifluorophenyl)hexanoate

HRID 706389Notes

Reaction equation

HRID 706389 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].[F:22][C:23]1[C:28]([F:29])=[CH:27][C:26]([F:30])=[CH:25][C:24]=1[CH2:31][C:32](=[O:34])[CH3:33].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.CS(C)=O.CCOC(C)=O>[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:16][CH:31]([C:24]1[CH:25]=[C:26]([F:30])[CH:27]=[C:28]([F:29])[C:23]=1[F:22])[C:32](=[O:34])[CH3:33])[C:10]([O:12][CH:13]([CH3:14])[CH3:15])=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 552746081-(2,3,5-Trifluorophenyl)propan-2-oneHCID 89815000isopropyl N-(tert-butoxycarbonyl)-O-(methylsulfonyl)serinate

Product 1

HCID 89815228Isopropyl 2-((tert-butoxycarbonyl)amino)-5-oxo-4-(2,3,5-trifluorophenyl)hexanoateYield 60%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2 (10.98 g, 33.7 mmol) in THF (50 mL) was added TEA (4.8 g, 47.4 mmol) 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 44 (6.3 g, 33.7 mmol) and Cs2CO3 (5.0 g, 15.3 mmol) in DMSO (35 mL) was added slowly crude 7 in DMSO (35 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 (50 mL) and extracted twice by MTBE. 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 45 (8.4 g, 60% yield). 1H NMR (DMSO-d6, 400 MHz): δ 6.77 (d, 1H), 6.59 (d, 1H), 5.11 (m, 1H), 4.93-4.89 (m, 1H), 4.12 (s, 2H), 2.66 (d, 1H), 2.05-2.01 (d, 3H), 1.38 (m, 9H), 1.18-1.15 (m, 6H); MS (ESI) m/e [M+H]+: 418.18.

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 (50 mL)
  5. extractionextracted twice by MTBE
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ea18243904fb49b28af34d66874667fa
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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