Toluene → (5-{4-[(1R,2S)-2-(2,2-Dichloro-acetylamino)-3-fluoro-1-hydroxy-propyl]-phenyl}-oxazol-2-ylmethyl)-carbamic acid tert-butyl ester

HRID 525549Notes

Reaction equation

HRID 525549 reaction equation
[C:1]([O:5][C:6](=[O:8])[NH2:7])([CH3:4])([CH3:3])[CH3:2].[Cl:9][CH:10]([Cl:29])[C:11]([NH:13][C@H:14]([CH2:27][F:28])[C@H:15]([OH:26])[C:16]1[CH:21]=[CH:20][C:19]([Sn](C)(C)C)=[CH:18][CH:17]=1)=[O:12].[F-].[Cs+].[C:32]1([CH3:38])C=CC=CC=1>O.[Cu]I>[C:1]([O:5][C:6](=[O:8])[NH:7][CH2:10][C:11]1[O:12][C:32]([C:19]2[CH:20]=[CH:21][C:16]([C@@H:15]([OH:26])[C@H:14]([NH:13][C:11](=[O:12])[CH:10]([Cl:29])[Cl:9])[CH2:27][F:28])=[CH:17][CH:18]=2)=[CH:38][N:13]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 25953Cesium fluorideHCID 77922tert-Butyl carbamateHCID 866953832,2-Dichloro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)-ethyl]-acetamide

Product 1

HCID 86695438(5-{4-[(1R,2S)-2-(2,2-Dichloro-acetylamino)-3-fluoro-1-hydroxy-propyl]-phenyl}-oxazol-2-ylmethyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 5-Bromo-oxazol-2-ylmethyl)-carbamic acid tert-butyl ester (0.035 g, 0.13 mmol) and 2,2-Dichloro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)-ethyl]acetamide (0.05 g, 0.11 mmol) in dry toluene (2.0 mL) is added CsF (0.034 g, 0.22 mmol) followed by CuI (0.002 g, 0.011 mmol) at room temperature. The resulting reaction mixture is degassed with nitrogen for 30 minutes then Pd2(PPh3)Cl2 (0.008 g, 0.011 mmol) is added and heated in microwave at 100° C. for 30 min. Reaction mixture is diluted with water and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, solvent is evaporated in vacuo and purified by column chromatography eluting in 10% methanol in CH2Cl2 follow by second purification using preparative HPLC to give the title compound (0.006 g, pure). LC-Ms (m/z): [M−H]=476.0.

Workup

  1. customThe resulting reaction mixture
  2. customis degassed with nitrogen for 30 minutes
  3. customReaction mixture
  4. extractionextracted with ethyl acetate
  5. dry with materialOrganic layer is dried over sodium sulphate, solvent
  6. customis evaporated in vacuo
  7. custompurified by column chromatography
  8. washeluting in 10% methanol in CH2Cl2
  9. customfollow by second purification

Sources & evidence

ORD record
ord-edfa91ddfdca41f8ac6aae2081d0fd3b
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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