Sodium Carbonate → HCID 86695524, compound

HRID 1487564Notes

Reaction equation

HRID 1487564 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].[C:30]([O:34][C:35](=[O:45])[NH:36][CH2:37][C:38]1[N:39]=[N:40][C:41](Cl)=[CH:42][CH:43]=1)([CH3:33])([CH3:32])[CH3:31].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:30]([O:34][C:35](=[O:45])[NH:36][CH2:37][C:38]1[N:39]=[N:40][C:41]([C:15]2[CH:16]=[CH:17][C:12]([C@H:8]3[O:7][C:6]([CH3:28])([CH3:27])[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:42][CH:43]=1)([CH3:33])([CH3:31])[CH3:32]

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 86695523HCID 86695523, compound

Product 1

HCID 86695524HCID 86695524, compoundYield 24.6%

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 (0.849 g, 2.058 mmol) and (6-Chloro-pyridazin-3-ylmethyl)-carbamic acid tert-butyl ester (0.5 g, 2.058 mmol) in toluene:ethanol:water (20:10:5 mL) is added Na2CO3 (0.436 g, 4.115 mmol) at room temperature. Resulting reaction mixture is degassed with nitrogen for 20 minutes followed by addition of Pd (PPh3)4 (0.237 g, 0.206 mmol). The resulting reaction mixture is heated to 80° C. for 16 h. Solvent is evaporated in vacuo and the crude material is diluted using water and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, concentrated and purified by using Combi-flash eluting with 20% MeOH in DCM to afford the title compound (0.250 g): 1H NMR (400 MHz, DMSO-d6) 1.40 (s, 9H), 1.53 (s, 3H), 1.61 (s, 3H), 3.94 (s, 1H), 4.47 (d, J=6.08 Hz, 2H), 4.58-4.59 (m, 0.5H), 4.70-4.71 (m, 1H), 4.83-4.84 (m, 0.5H), 4.94-4.97 (m, 1H), 5.30 (d, J=3.32 Hz, 1H), 6.65 (t, J=52.32 Hz, 1H), 7.61-7.67 (m, 4H), 8.18 (d, J=8.12 Hz, 2H), 8.24 (d, J=8.84 Hz, 1H). LC-MS (m/z): [M+H]=495.2.

Workup

  1. customResulting
  2. customreaction mixture
  3. customis degassed with nitrogen for 20 minutes
  4. customThe resulting reaction mixture
  5. customSolvent is evaporated in vacuo
  6. additionthe crude material is diluted
  7. extractionextracted with ethyl acetate
  8. dry with materialOrganic layer is dried over sodium sulphate
  9. concentrationconcentrated
  10. custompurified
  11. washeluting with 20% MeOH in DCM

Sources & evidence

ORD record
ord-3931733e7743480a8ff3a3d497cb13ef
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

Loading…