Triphenylphosphine → HCID 86622861, compound

HRID 1013127Notes

Reaction equation

HRID 1013127 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:19][CH2:20][C:21]([CH3:25])([CH3:24])[CH2:22]O.N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[N:19]1[CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20]1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 59799080HCID 59799080, compound

Product 1

HCID 86622861HCID 86622861, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve 7-chloro-6-(3-hydroxy-2,2-dimethyl-propylamino)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (prepared as described in Preparation 30) (250 mg, 0.66 mmol) in DCM (30 mL). Add diethyl azodicarboxylate (150 mg, 0.86 mmol), and triphenylphosphine (226 mg, 0.86 mmol) and stir at 40° C. for 16 h. Quench with saturated aqueous sodium bicarbonate solution, extract with DCM three times. Combine the organic layers, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 1:8 EtOAc:hexanes) to provide 7-chloro-6-(3,3-dimethylazetidin-1-yl)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (175 mg, 74%). MS (ES) m/z:=361.2 [M+H]. Deprotection and the succinate salt formation of the free amine is achieved essentially as described in Example 34 to give the title compound (91 mg, 71%).

Workup

  1. customQuench with saturated aqueous sodium bicarbonate solution
  2. extractionextract with DCM three times
  3. dry with materialCombine the organic layers, dry (sodium sulfate)
  4. concentrationconcentrate
  5. custompurify
  6. wash(silica gel chromatography, eluting with 1:8 EtOAc:hexanes)

Sources & evidence

ORD record
ord-dcc80788e4d442fdaec4a001e34b4e0e
Source dataset
uspto-grants-2011_07
Patent number
US07981882B2

Reaction notes

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