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Sodium Carbonate → 2,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-5-[4-(6-hydroxy-methyl-pyridin-3-yl)-phenyl]-2,2-dimethyl-oxazolidin-3-yl}-ethanone

HRID 1487473
Notes
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Reaction equation

HRID 1487473 reaction equation
[F:1][CH:2]([F:29])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:28])[CH3:27])=[O:4].Br[C:31]1[CH:32]=[CH:33][C:34]([CH2:37]O)=[N:35][CH:36]=1.C([O-])([O-])=[O:40].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:29][CH:2]([F:1])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:33]3[C:34]([CH3:37])=[N:35][C:36]([OH:40])=[CH:31][CH:32]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:27])[CH3:28])=[O:4]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 5200169(5-Bromopyridin-2-yl)methanolHCID 866954142,2-difluoro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-3-yl)ethanone

Product 1

HCID 1784334402,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-5-[4-(6-hydroxy-methyl-pyridin-3-yl)-phenyl]-2,2-dimethyl-oxazolidin-3-yl}-ethanoneYield 35.1%

Reagents, catalysts & solvents

4
HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 2,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidin-3-yl}-ethanone (2.0 g, 4.843 mmol) in toluene (40 mL), ethanol (10 mL), water (10 mL) and (5-Bromo-pyridin-2-yl)-methanol (0.91 g, 4.843 mmol) is added Na2CO3 (1.54 g, 14.528 mmol) at room temperature. Resulting reaction mixture is degassed with nitrogen for 30 minutes then Pd(PPh3)4 (0.559 g, 0.484 mmol) is added. The reaction mixture is heated to 90° C. for 6 hours. Solvent is evaporated in vacuo then diluted with water and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, solvent is evaporated in vacuo and purified by combi-flash chromatography using 80% ethyl acetate in hexane as an eluent to afford the title compound (0.67 g): 1H-NMR (400 MHz, CDCl3) δ: 1.53 (s, 3H), 1.60 (S, 3H), 4.54-4.58 (m, 0.5H), 4.60 (d, J=5.84 Hz, 2H), 4.66-4.72 (m, 1H), 4.81-4.84 (m, 0.5H), 4.90-4.94 (m, 1H), 5.26 (d, J=3.72 Hz, 1H), 5.48 (t, J=5.8 Hz, 1H), 6.64 (t, J=52.4 Hz, 1H), 7.55-7.64 (m, 3H), 7.78 (d, J=8.2 Hz, 2H), 8.09-8.12 (dd, J=2.32 Hz, J=8.16 Hz, 1H), 8.81 (d, 2.04 Hz, 1H). LC-MS (m/z): [M+H]=395.0.

Workup

  1. customResulting
  2. customreaction mixture
  3. customis degassed with nitrogen for 30 minutes
  4. customSolvent is evaporated in vacuo
  5. additionthen diluted with water
  6. extractionextracted with ethyl acetate
  7. dry with materialOrganic layer is dried over sodium sulphate, solvent
  8. customis evaporated in vacuo
  9. custompurified by combi-flash chromatography

Sources & evidence

ORD record
ord-949c18dbd2a54b8980f1ccbf24979a30
Source dataset
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09428528B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes