Sodium Carbonate → (4S,5R)-tert-butyl 5-(4-(6-(1,1-dioxido-2H-thiet-3-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 1500299Notes

Reaction equation

HRID 1500299 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2(F)[CH2:11][S:10](=[O:13])(=[O:12])[CH2:9]2)=[N:6][CH:7]=1.[C:15]([O:19][C:20]([N:22]1[C@H:26]([CH2:27][F:28])[C@@H:25]([C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)[O:24][C:23]1([CH3:45])[CH3:44])=[O:21])([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])[O-].[Na+].[Na+]>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.C1(C)C=CC=CC=1.C(O)C.O>[O:12]=[S:10]1(=[O:13])[CH:11]=[C:8]([C:5]2[N:6]=[CH:7][C:2]([C:32]3[CH:31]=[CH:30][C:29]([C@H:25]4[O:24][C:23]([CH3:44])([CH3:45])[N:22]([C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21])[C@@H:26]4[CH2:27][F:28])=[CH:34][CH:33]=3)=[CH:3][CH:4]=2)[CH2:9]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58631114(4S,5R)-Rel-tert-butyl4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidine-3-carboxylateHCID 867131853-(5-Bromopyridin-2-yl)-3-fluorothietane 1,1-dioxide

Product 1

HCID 86713187(4S,5R)-tert-butyl 5-(4-(6-(1,1-dioxido-2H-thiet-3-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
80 °C

Procedure

The solution of the product of step 3, Example 18 (0.15 g, 0.538 mmol, 1 eq), (4S,5R)-4-Fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidine-3-carboxylic acid tert-butyl ester (previously described in US2004082553, Example 20, intermediate 19, 0.234 g, 0.538 mmol, 1 eq) and sodium carbonate (0.171 g, 1.613 mmol, 3 eq) in mixture of Toluene/Ethanol/Water (1:1:0.5, 2.5 mL) is degassed with nitrogen for 30 minutes in sealed tube. To the resulting reaction mixture tetrakis(triphenylphosphine)palladium(0) (0.062 g, 0.054 mmol, 0.1 eq) is added. Resulting reaction mixture is heated at 80° C. for 6 hours. The reaction mixture is quenched with water (15 mL) and extracted with ethyl acetate (3×25 mL). Combined organic layer is dried over sodium sulphate and concentrated in vacuo. The crude compound is purified by column chromatography using (100-200 mesh silica). Desired compound is eluted with 30% ethyl acetate in hexane to afford title compound as yellow solid (0.16 g): 1H-NMR (400 MHz, DMSO) δ: 1.43 (bs, 9H), 1.51 (s, 3H), 1.64 (s, 3H), 3.85-3.90 (m, 1H), 4.47-4.59 (m, 1H), 4.75-4.84 (m, 1H), 5.05 (s, 2H), 5.15 (d, 1H, J=7.16 Hz), 7.62 (d, 2H, J=8.12 Hz), 7.76 (s, 1H), 7.87 (d, 2H, J=8.2 Hz), 7.93 (d, 1H, J=8.12 Hz), 8.31-8.34 (dd, 1H, J1=8.24 Hz, J2=2.16 Hz). 9.07 (d, 1H, J=1.88 Hz). LC-MS (m/z): [M+H] 489.1.

Workup

  1. customis degassed with nitrogen for 30 minutes in sealed tube
  2. additionis added
  3. customResulting
  4. customreaction mixture
  5. customThe reaction mixture is quenched with water (15 mL)
  6. extractionextracted with ethyl acetate (3×25 mL)
  7. dry with materialCombined organic layer is dried over sodium sulphate
  8. concentrationconcentrated in vacuo
  9. customThe crude compound is purified by column chromatography
  10. washDesired compound is eluted with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-092e41b5151449aca5db6bb7b359ffc3
Source dataset
uspto-grants-2015_12
Patent number
US09206126B2

Reaction notes

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