2-(Di-tert-butylphosphino)biphenyl → HCID 67443331, compound

HRID 1666689Notes

Reaction equation

HRID 1666689 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[C:4]([CH3:14])[N:3]=1.[NH2:15][CH:16]1[CH:20]([F:21])[CH2:19][N:18]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:17]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1>[F:21][CH:20]1[CH:16]([NH:15][C:2]2[N:3]=[C:4]([CH3:14])[CH:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=2)[CH2:17][N:18]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:19]1

Participants

7

Reactant 4

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 31569994-(2-chloro-6-methylpyrimidin-4-yl)morpholineHCID 23676156Sodium t-butoxideHCID 59825231HCID 59825231, compound

Product 1

HCID 67443331HCID 67443331, compoundYield 7.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 4-(2-chloro-6-methylpyrimidin-4-yl)morpholine (180 mg), benzyl (3RS,4RS)-3-amino-4-fluoropyrrolidine-1-carboxylate (240 mg), Pd(OAc)2 (38 mg), 2-(di-t-butylphosphino)biphenyl (0.10 g), sodium t-butoxide (0.24 g), and toluene (2 mL) was heated to reflux under nitrogen atmosphere for 6 h. The reaction solution was extracted with chloroform and dried with anhydrous magnesium sulfate. The desiccant was removed by filtration, then the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=1:2) to obtain benzyl (3RS,4RS)-3-fluoro-4-(4-methyl-6-morpholin-4-ylpyrimidin-2-ylamino)pyrrolidine-1-carboxylate (25 mg).

Workup

  1. temperaturewas heated
  2. temperatureto reflux under nitrogen atmosphere for 6 h
  3. extractionThe reaction solution was extracted with chloroform
  4. dry with materialdried with anhydrous magnesium sulfate
  5. customThe desiccant was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=1:2)

Sources & evidence

ORD record
ord-18306e11c36e42c88c318288e4c3b338
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

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