Dichloromethane → (5-{4-[(4S,5R)-3-(2,2-Difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl ester

HRID 525622Notes

Reaction equation

HRID 525622 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:43]=[CH:42][C:41](Cl)=[CH:40][N:39]=1)([CH3:33])([CH3:32])[CH3:31].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>C(O)(C)C.O>[C:30]([O:34][C:35](=[O:45])[NH:36][CH2:37][C:38]1[N:43]=[CH:42][C:41]([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:29])[F:1])[C@@H:9]3[CH2:10][F:11])=[CH:13][CH:14]=2)=[CH:40][N:39]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 72710400tert-Butyl ((5-chloropyrimidin-2-yl)methyl)carbamateHCID 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 86695517(5-{4-[(4S,5R)-3-(2,2-Difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl esterYield 36.4%

Reagents, catalysts & solvents 1

HCID 21889133Propan-2-ol--water (1/1)Solvent

Conditions

Temperature
140 °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 (0.286 g, 0.694 mmol) and (5-Chloro-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl ester (0.2 g, 0.694 mmol) in isopropylalcohol:water (2:1, 6 mL) is added K2CO3 (0.287 g, 2.083 mmol) at room temperature. Resulting reaction mixture is degassed with nitrogen for 20 minutes followed by addition of Pd(dppf)Cl2.CH2Cl2 (0.028 g, 0.035 mmol). The resulting reaction mixture is heated to 140° C. for 20 minutes in a microwave. 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 column chromatography using Combi-flash eluting with 75% ethyl acetate in hexane to afford the title compound (0.125 g): 1H NMR (400 MHz, DMSO-d6) δ: 1.40 (s, 9H), 1.52 (s, 3H), 1.60 (s, 3H), 4.36 (d, J=6.16 Hz, 2H), 4.54-4.58 (m, 0.5H), 4.66-4.73 (m, 1H), 4.82-4.85 (m, 0.5H), 4.91-4.95 (m, 1H), 5.28 (d, J=3.52 Hz, 1H), 6.64 (t, J=52.44 Hz, 1H), 7.32 (t, J=6.04 Hz, 1H), 7.62 (d, J=8.04 Hz, 2H), 7.86 (d, J=8.04 Hz, 2H), 9.10 (s, 2H). LC-MS (m/z): [M+H]=495.

Workup

  1. customResulting
  2. customreaction mixture
  3. customis degassed with nitrogen for 20 minutes
  4. additionfollowed by addition of Pd(dppf)Cl2
  5. customThe resulting reaction mixture
  6. customSolvent is evaporated in vacuo
  7. additionthe crude material is diluted
  8. extractionextracted with ethyl acetate
  9. dry with materialOrganic layer is dried over sodium sulphate
  10. concentrationconcentrated
  11. custompurified by column chromatography
  12. washeluting with 75% ethyl acetate in hexane

Sources & evidence

ORD record
ord-f61b196d76634dcabc1e9d7d6a99a645
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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