Cesium carbonate → HCID 67188186, compound

HRID 1441974Notes

Reaction equation

HRID 1441974 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:20]([F:23])=[CH:21][CH:22]=1)[CH2:5][C@@H:6]([C:16]([O:18][CH3:19])=[O:17])[N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH3:8].[CH3:24][Si:25]([CH3:68])([CH3:67])[CH2:26][CH2:27][O:28][C:29](=[O:66])[C@H:30]([CH2:42][C:43]1[CH:48]=[C:47](B2OC(C)(C)C(C)(C)O2)[CH:46]=[CH:45][C:44]=1[O:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)[NH:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.ClCCl>[CH2:59]([O:58][C:44]1[CH:45]=[CH:46][C:47]([C:2]2[CH:22]=[CH:21][C:20]([F:23])=[C:4]([CH2:5][C@H:6]([N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH3:8])[C:16]([O:18][CH3:19])=[O:17])[CH:3]=2)=[CH:48][C:43]=1[CH2:42][C@H:30]([NH:31][C:32]([O:34][CH2:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:33])[C:29](=[O:66])[O:28][CH2:27][CH2:26][Si:25]([CH3:68])([CH3:67])[CH3:24])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 67186122HCID 67186122, compoundHCID 69226354HCID 69226354, compound

Product 1

HCID 67188186HCID 67188186, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution of 1.68 g (4.09 mmol) of methyl 3-bromo-N-(tert-butoxycarbonyl)-6-fluoro-N-methyl-L-phenylalaninate (Example 14O) in 8 ml of 1-methyl-2-pyrrolidone is rendered inert and saturated with argon (pass argon through for about 30 min). Then 334 mg (0.41 mmol) of bis(diphenylphosphino)ferrocenepalladium(II)chloride (PdCI2(dppf)) are added, and the mixture is stirred at RT for 10 min. Thereafter, 3.45 g (4.92 mmol) of 2-(trimethylsilyl)ethyl-2-(benzyloxy)-N-[(benzyloxy)carbonyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-L-phenylalaninate (Example 16A) in 8 ml of 1-methyl-2-pyrrolidone and 2.67 g (8.19 mmol) of cesium carbonate are added. A gentle stream of argon is passed over the reaction mixture, which is stirred at 50° C. for 20 h. The mixture is cooled, taken up in dichloromethane and washed with water. The organic phase is dried over magnesium sulfate, and the solvent is concentrated in vacuo. The residue is purified by column chromatography on silica gel (cyclohexane:ethyl acetate 7:3).

Workup

  1. customis rendered inert and saturated with argon (pass argon through for about 30 min)
  2. stirringis stirred at 50° C. for 20 h
  3. temperatureThe mixture is cooled
  4. washwashed with water
  5. dry with materialThe organic phase is dried over magnesium sulfate
  6. concentrationthe solvent is concentrated in vacuo
  7. customThe residue is purified by column chromatography on silica gel (cyclohexane:ethyl acetate 7:3)

Sources & evidence

ORD record
ord-67af5242fad744b698d7ebbdebcd9128
Source dataset
uspto-grants-2010_02
Patent number
US07655643B2

Reaction notes

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