Triphenylphosphine → HCID 24829863, compound

HRID 1435128Notes

Reaction equation

HRID 1435128 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[S:14][C:13]([C:15](OC)=[O:16])=[C:12]([O:19][C@@H:20]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[C:23]=4[Cl:29])[CH3:21])[CH:11]=3)[C:6]=2[CH:30]=1.[CH3:32][N:33]1[CH2:38][CH2:37][CH:36](O)[CH2:35][CH2:34]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/[N:66]=N/C(OC(C)(C)C)=O)=O)(C)C>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:31])=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[S:14][C:13]([C:15]([NH2:66])=[O:16])=[C:12]([O:19][C@@H:20]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH:36]5[CH2:37][CH2:38][N:33]([CH3:32])[CH2:34][CH2:35]5)[C:23]=4[Cl:29])[CH3:21])[CH:11]=3)[C:6]=2[CH:30]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 660484-Piperidinol, 1-methyl-HCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 57937608HCID 57937608, compound

Product 1

HCID 24829863HCID 24829863, compoundYield 608.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 5-(6-chloro-5-fluoro-1H-benzimidazol-1-yl)-3-{[(1R)-1-(2-chloro-3-hydroxyphenyl)ethyl]oxy}-2-thiophenecarboxylate (Example 69, Step E, 0.10 g, 0.21 mmol) and 1-methyl-4-piperidinol (0.05 g, 0.42 mmol) in DCM (2 mL) was added polymer-supported triphenylphosphine (0.19 g, 0.42 mmol), di-tert-butylazodicarboxylate (0.10 g, 0.42 mmol). The reaction mixture was stirred for 8 h. The reaction was filtered with DCM washings and the volatiles were evaporated under reduced pressure. To the residue was added a solution of 7 N ammonia in MeOH (8 mL). The mixture was heated in a sealed tube to 70° C. for 48 h and then cooled to rt. Silica; was added and the volatiles evaporated under reduced pressure and the residue was purified by flash chromatography ((0 to 100% 89/10/1 DCM/MeOH/ammonium hydroxide:DCM) to afford 0.72 g (61%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 7.86 (d, J=9.7 Hz, 1H), 7.84 (s, 1H), 7.72 (d, J=6.4 Hz, 1H), 7.33 (t, J=8.0 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.17 (s, 1H), 7.15 (d, J=8.2 Hz, 1H), 7.13 (s, 1H), 6.00 (q, J=6.0 Hz, 1H), 4.45 (s, 1H), 2.51-2.62 (m, 2H), 2.15-2.25 (m, 2H), 2.13 (s, 3H), 1.78-1.93 (m, 2H), 1.70 (d, J=6.4 Hz, 3H), 1.56-1.67 (m, 2H). MS (ESI): 564 [M+H]+.

Workup

  1. filtrationThe reaction was filtered with DCM washings
  2. customthe volatiles were evaporated under reduced pressure
  3. additionTo the residue was added a solution of 7 N ammonia in MeOH (8 mL)
  4. temperaturecooled to rt
  5. additionwas added
  6. customthe volatiles evaporated under reduced pressure
  7. customthe residue was purified by flash chromatography ((0 to 100% 89/10/1 DCM/MeOH/ammonium hydroxide:DCM)

Sources & evidence

ORD record
ord-ec06787cbb9b4de29297ba31ce9a5692
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

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