Triphenylphosphine → HCID 68569280, compound

HRID 1435126Notes

Reaction equation

HRID 1435126 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]([O:11][C:12]1[CH:16]=[C:15]([N:17]2[C:21]3[CH:22]=[CH:23][C:24]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:25][C:20]=3[N:19]=[CH:18]2)[S:14][C:13]=1[C:31]([O:33][CH3:34])=[O:32])[CH3:10].[CH3:35][N:36]1[CH2:41][CH2:40][CH:39](O)[CH2:38][CH2:37]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C(Cl)Cl>[Cl:1][C:2]1[C:7]([O:8][CH:39]2[CH2:40][CH2:41][N:36]([CH3:35])[CH2:37][CH2:38]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]([O:11][C:12]1[CH:16]=[C:15]([N:17]2[C:21]3[CH:22]=[CH:23][C:24]([O:26][C:27]([F:29])([F:30])[F:28])=[CH:25][C:20]=3[N:19]=[CH:18]2)[S:14][C:13]=1[C:31]([O:33][CH3:34])=[O:32])[CH3:10]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 660484-Piperidinol, 1-methyl-HCID 97268Di-tert-butyl azodicarboxylateHCID 57937552HCID 57937552, compound2×

Product 1

HCID 68569280HCID 68569280, compoundYield 97.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a slurry of methyl 3-{[(1R)-1-(2-chloro-3-hydroxyphenyl)ethyl]oxy}-5-{5-[(trifluoromethyl)oxy]-1H-benzimidazol-1-yl}-2-thiophenecarboxylate (Intermediate 25, 0.18 g, 0.35 mmol) and 1-methyl-4-piperidinol (0.12 g, 1.1 mmol) in DCM (10 mL) was added triphenylphosphine (0.18 g, 0.70 mmol) and di-tert-butyl azodicarboxylate (0.16 g, 0.70 mmol). The clear, yellow solution was stirred for 1 h, and then silica gel (3 g) was added. The volatiles were evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 100% 80/20/1 DCM/MeOH/ammonium hydroxide:DCM) to give 0.20 g (0.34 mmol) of methyl 3-[((1R)-1-{2-chloro-3-[(1-methyl-4-piperidinyl)oxy]phenyl}ethyl)oxy]-5-{5-[(trifluoromethyl)oxy]-1H-benzimidazol-1-yl}-2-thiophenecarboxylate which was then dissolved in a solution of 7 N ammonia in MeOH (10 mL). The mixture was heated in a sealed tube to 80° C. for 40 h and then cooled to rt. Silica (1 g) was added, the volatiles were evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 100% 80/20/1 DCM/MeOH/ammonium hydroxide:DCM) to afford 0.18 g (86%) of the title compound as a light yellow solid. 1H NMR (400 MHz, CD3OD): δ 8.45 (s, 1H), 7.63 (s, 1H), 7.45 (d, J=8.79 Hz, 1H), 7.31 (m, 2H), 7.17 (d, J=7.51 Hz, 1H), 7.10 (d, J=8.24 Hz, 1H), 6.97 (s, 1H), 6.05 (q, J=6.29 Hz, 1H), 4.56 (m, 3H), 2.72 (br m, 2H), 2.47 (br m, 2H), 2.33 (s, 3H), 1.95 (br m, 4H), 1.77 (d, J=6.41 Hz, 3H): MS (ESI): 595 [M+H]+.

Workup

  1. additionsilica gel (3 g) was added
  2. customThe volatiles were evaporated under reduced pressure
  3. customthe residue was purified by flash column chromatography (0 to 100% 80/20/1 DCM/MeOH/ammonium hydroxide:DCM)

Sources & evidence

ORD record
ord-a5e9fb61c366437fb4c196466f98c586
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

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