Sodium Carbonate → HCID 86695521, compound

HRID 1487562Notes

Reaction equation

HRID 1487562 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]([CH:37]([NH:41][S:42]([C:44]([CH3:47])([CH3:46])[CH3:45])=[O:43])[CH2:38][C:39]#[N:40])=[N:35][CH:36]=1.C([O-])([O-])=O.[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>[C:39]([CH2:38][CH:37]([NH:41][S:42]([C:44]([CH3:47])([CH3:46])[CH3:45])=[O:43])[C:34]1[CH:33]=[CH:32][C:31]([C:15]2[CH:16]=[CH:17][C:12]([C@H:8]3[O:7][C:6]([CH3:27])([CH3:28])[N:5]([C:3](=[O:4])[CH:2]([F:1])[F:29])[C@@H:9]3[CH2:10][F:11])=[CH:13][CH:14]=2)=[CH:36][N:35]=1)#[N:40]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 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)ethanoneHCID 86695520HCID 86695520, compound

Product 1

HCID 86695521HCID 86695521, compoundYield 51.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
80 °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 (0.312 g, 0.758 mmol) and 2-Methyl-propane-2-sulfinic acid [1-(5-bromo-pyridin-2-yl)-2-cyano-ethyl]-amide (0.25 g, 0.758 mmol) in toluene:Ethanol:water (10:10:10 mL) is added Na2CO3 (0.16 g, 1.515 mmol) at room temperature. Resulting reaction mixture is degassed with nitrogen for 15 minutes followed by addition of Pd(PPh3)4 (0.087 g, 0.076 mmol). Resulting reaction mixture is heated to 80° C. for 3 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 50% ethyl acetate in hexane to afford the title compound (0.21 g): 1H-NMR (400 MHz, DMSO-d6) δ: 1.19 (s, 9H), 1.53 (s, 3H), 1.60 (S, 3H), 2.98-3.04 (m, 1H), 3.17-3.22 (m, 1H), 4.54-4.58 (m, 0.5H), 4.66-4.70 (m, 1H), 4.78-4.84 (m, 1.5H), 4.89-4.95 (m, 1H), 5.26-5.27 (m, 1H), 6.12 (d, J=9 Hz, 1H), 6.64 (t, J=52.4 Hz, 1H), 7.53-7.64 (m, 2H), 7.76 (d, J=8.2 Hz, 1H), 7.82 (d, J=8.12 Hz, 2H), 8.89 (d, J=1.84 Hz, 1H), 8.86 (d, J=2.08 Hz, 1H). LC-MS (m/z): [M+H]=537.2.

Workup

  1. customResulting
  2. customreaction mixture
  3. customis degassed with nitrogen for 15 minutes
  4. customResulting
  5. customreaction mixture
  6. customSolvent is evaporated in vacuo
  7. additionthen diluted with water
  8. extractionextracted with ethyl acetate
  9. dry with materialOrganic layer is dried over sodium sulphate, solvent
  10. customis evaporated in vacuo
  11. custompurified by combi-flash chromatography

Sources & evidence

ORD record
ord-6826c611605c4f5c8c76da9ad931302f
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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