Cesium carbonate → HCID 89515146, compound

HRID 2283177Notes

Reaction equation

HRID 2283177 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([C:15]3([NH:18]C(=O)OC(C)(C)C)[CH2:17][CH2:16]3)[CH:12]=[CH:13][CH:14]=2)O1.[Cl:27][CH:28]([Cl:47])[C:29]([N:31]1[C@H:35]([CH2:36][F:37])[C@@H:34]([C:38]2[CH:43]=[CH:42][C:41](I)=[CH:40][CH:39]=2)[O:33]C1(C)C)=[O:30].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1(C)C=CC=CC=1.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>[NH2:18][C:15]1([C:11]2[CH:10]=[C:9]([C:41]3[CH:42]=[CH:43][C:38]([C@@H:34]([OH:33])[C@H:35]([NH:31][C:29](=[O:30])[CH:28]([Cl:27])[Cl:47])[CH2:36][F:37])=[CH:39][CH:40]=3)[CH:14]=[CH:13][CH:12]=2)[CH2:16][CH2:17]1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 59166267tert-butyl (1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropyl)carbamateHCID 86695394(4S,5R)-3-(dichloroacetyl)-4-(fluoromethyl)-5-(4-iodophenyl)-2,2-dimethyl-1,3-oxazolidine

Product 1

HCID 89515146HCID 89515146, compoundYield 21.7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl (1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropyl)carbamate (241 mg, 0.672 mmol), 2,2-dichloro-1-((4S,5R)-4-(fluoromethyl)-5-(4-iodophenyl)-2,2-dimethyloxazolidin-3-yl)ethanone (250 mg, 0.56 mmol), Cs2CO3 (365 mg, 1.12 mmol) in dioxane (4 mL) and water (1 mL) is bubbled with nitrogen gas for 2 minutes. Pd(PPh3)4 (64 mg, 0.056 mmol) is added and the resulting reaction mixture heated at 80° C. for 4 hours. Reaction is diluted with water (10 ml) and extracted with ethyl acetate (3×10 mL). Combined organic solution is dried over Na2SO4 and concentrated. Crude compound dissolved in DCM (3 mL) and stirred with TFA (0.6 mL) at room temperature for 1 hour. Reaction is diluted with toluene (10 mL) and concentrated. Crude compound is basified slowly using saturated aq. NaHCO3, extracted with ethyl acetate (3×30 mL) and combined extracts dried over Na2SO4 and concentrated. Solid dissolved in DMF (2 mL) and purified using HPLC eluting from 5 to 95% water/acetonitrile to give the title compound (50 mg): 1 HNMR (400 MHz, MeOH-d4) δ: 1.33-1.39 (m, 2H), 1.40-1.47 (m, 2H), 4.33-4.42 (m, 1.5H), 4.44-4.51 (m, 0.5H) 4.56-4.63 (m, 0.5H), 4.68-4.75 (m, 0.5H), 5.03 (d, 1H, J=4 Hz), 6.31 (s, 1H), 7.44-7.48 (m, 1H), 7.50-5.55 9 m, 3H), 7.63-7.68 (m, 3H), 7.75-7.78 (m, 1H), m/z (Cl) 411 [M+1].

Workup

  1. customis bubbled with nitrogen gas for 2 minutes
  2. customthe resulting reaction mixture
  3. customReaction
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. dry with materialCombined organic solution is dried over Na2SO4
  6. concentrationconcentrated
  7. dissolutionCrude compound dissolved in DCM (3 mL)
  8. customReaction
  9. concentrationconcentrated
  10. extractionextracted with ethyl acetate (3×30 mL)
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. dissolutionSolid dissolved in DMF (2 mL)
  14. custompurified
  15. washeluting from 5 to 95% water/acetonitrile

Sources & evidence

ORD record
ord-e3f032e5ccb14d67baae3ef4b1309031
Source dataset
uspto-grants-2015_09
Patent number
US09145355B2

Reaction notes

Loading…