Ethylamine → (4S,5R)-5-[4-(6-Ethylcarbamoyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylicacid tert-butyl ester

HRID 1487516Notes

Reaction equation

HRID 1487516 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[CH:23][C:24]([C:27]([OH:29])=O)=[N:25][CH:26]=3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:32]([NH2:34])[CH3:33].C(NC(C)C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[N:25][C:24]([C:27](=[O:29])[NH:34][CH2:32][CH3:33])=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

8

Reactant 4

HCID 6341EthylamineHCID 7912DiisopropylamineHCID 11776TriphenylphosphineHCID 866954625-[4-((4S,5R)-3-tert-Butoxycarbonyl-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl)-phenyl]-pyridine-2-carboxylic acid

Product 1

HCID 86695463(4S,5R)-5-[4-(6-Ethylcarbamoyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylicacid tert-butyl esterYield 65.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred solution of 5-[4-((4S,5R)-3-tert-Butoxycarbonyl-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl)-phenyl]-pyridine-2-carboxylic acid (0.3 g, 0.697 mmol) in dry tetrahydrofuran (5 mL) is added ethyl amine (0.038 g, 0.837 mmol), diisopropylamine (0.27 g, 2.092 mmol) and 50% solution of triphenyl phosphine in ethyl acetate (0.332 g, 0.66 mL, 1.046 mmol) and stirred at room temperature for 14 hours. Diluted with water and ethyl acetate, organic layer is separated and aqueous layer is extracted with ethyl acetate. Combined organic layer is dried over sodium sulphate, solvent is evaporated in vacuo to obtained crude material purified by column chromatography eluting in 3% methanol in CH2Cl2 to afford title compound (0.21 g): 1H-NMR (400 MHz, DMSO-d6): δ: 1.13 (t, 3H, J=6.98 Hz), 1.44 (s, 9H), 1.51 (s, 3H), 1.64 (s, 3H), 3.34-3.37 (m, 2H), 3.84-3.91 (m, 1H), 4.47-4.59 (m, 1H), 4.76-4.95 (m, 2H), 5.15 (d, 1H, J=7.24 Hz), 7.61 (d, 2H, J=8.28 Hz), 7.83 (d, 2H, J=8.24 Hz), 8.09 (d, 1H, J=8.20 Hz), 8.29 (dd, 1H, J=8.08 Hz, J=2.2 Hz), 8.84 (t, 1H, J=5.68 Hz), 8.93 (d, 1H, J=1.88 Hz) LC-MS (m/z): [M+H]=458.1.

Workup

  1. customis separated
  2. extractionaqueous layer is extracted with ethyl acetate
  3. dry with materialCombined organic layer is dried over sodium sulphate, solvent
  4. customis evaporated in vacuo
  5. customto obtained crude material
  6. custompurified by column chromatography
  7. washeluting in 3% methanol in CH2Cl2

Sources & evidence

ORD record
ord-a799fcda12f043559bb91992bd14d646
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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