2,2,2-Trifluoroethyl trifluoromethanesulfonate → tert-Butyl((5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl)carbamate

HRID 706391Notes

Reaction equation

HRID 706391 reaction equation
[CH3:1][C@H:2]1[NH:7][C:6](=[O:8])[CH:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:4][C@H:3]1[C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[C:18]=1[F:25].CN1C(=O)N(C)CCC1.C(O[Li])(C)(C)C.[C:41]([CH2:45]OS(C(F)(F)F)(=O)=O)([F:44])([F:43])[F:42]>C1COCC1>[CH3:1][C@H:2]1[N:7]([CH2:45][C:41]([F:44])([F:43])[F:42])[C:6](=[O:8])[CH:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:14])([CH3:15])[CH3:13])[CH2:4][C@H:3]1[C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[C:19]([F:24])[C:18]=1[F:25]

Participants

6

Reactant 4

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 89821830tert-Butyl ((5S,6R)-6-methyl-2-oxo-5-(2,3,5-trifluorophenyl)piperidin-3-yl)carbamateHCID 178506942HCID 178506942, compound

Product 1

HCID 89821823tert-Butyl((5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl)carbamateYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22.5 °C

Procedure

To a solution of 46 (50 g, 0.14 mol) and DMPU (7.2 g, 0.06 mol) in THF (500 mL) was added tert-BuOLi (8.6 g, 0.11 mol) in portions at 20° C. for 0.5 h. After the mixture was degassed for 30 min at 20° C., CF3CH2OTf (37.5 g, 0.14 mol) was added at 20-25° C. The solution was stirred for 24 h at 20-25° C. After the reaction was complete, the mixture was quenched by water, and then partitioned with water and EtOAc. The organic solution was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE) to give product 47 (50 g, 82% yield). 1H (DMSO-d6, 400 MHz): δ 7.52 (m, 1H), 7.22-6.91 (m, 1H), 4.65 (m, 1H), 3.85 (br, 1H), 3.38-3.37 (m, 2H), 1.40 (s, 9H), 0.90 (m, 3H); MS (ESI) m/e [M+H]+: 441.15.

Workup

  1. customAfter the mixture was degassed for 30 min at 20° C.
  2. customthe mixture was quenched by water
  3. custompartitioned with water and EtOAc
  4. dry with materialThe organic solution was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE)

Sources & evidence

ORD record
ord-2ee09478e079453f9cc17ab442a116f6
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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