Triphenylphosphine → HCID 69014199, compound

HRID 1435125Notes

Reaction equation

HRID 1435125 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].O[CH:36]1[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>C(Cl)Cl>[Cl:1][C:2]1[C:3]([C@H:9]([O:11][C:12]2[CH:16]=[C:15]([N:17]3[C:21]4[CH:22]=[CH:23][C:24]([O:26][C:27]([F:29])([F:30])[F:28])=[CH:25][C:20]=4[N:19]=[CH:18]3)[S:14][C:13]=2[C:31]([O:33][CH3:34])=[O:32])[CH3:10])=[CH:4][CH:5]=[CH:6][C:7]=1[O:8][CH:36]1[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 57937552HCID 57937552, compound2×

Product 1

HCID 69014199HCID 69014199, compoundYield 82.9%

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 1,1-dimethylethyl 4-hydroxy-1-piperidinecarboxylate (0.21 g, 1.0 mmol) in DCM (10 mL) was added triphenylphosphine (0.18 g, 0.70 mmol) and di-tert-butylazodicarboxylate (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 50% EtOAc:CH2Cl2) to give 0.20 g (0.29 mmol) of 1,1-dimethylethyl 4-[(2-chloro-3-{(1R)-1-[(2-[(methyloxy)carbonyl]-5-{5-[(trifluoromethyl)oxy]-1H-benzimidazol-1-yl}-3-thienyl)oxy]ethyl}phenyl)oxy]-1-piperidinecarboxylate which was then dissolved in 5 mL of DCM and TFA (1 mL, 5.9 mmol) was added. After 1 h the volatiles were evaporated under reduced pressure and the residue was 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 0.14 g (69%) of the title compound as a light yellow solid. 1H NMR (400 MHz, CD3OD): δ 8.45 (s, 1H), 7.63 (s, 1H), 7.42 (d, J=8.79 Hz, 1H), 7.30 (m, 2H), 7.15 (d, J=7.87 Hz, 1H), 7.10 (d, J=7.87 Hz, 1H), 6.97 (s, 1H), 6.05 (q, J=6.29 Hz, 1H), 4.56 (m, 3H), 3.06 (m, 2H), 2.69 (m, 2H), 1.95 (m, 2H), 1.77 (d, J=6.23 Hz, 3H), 1.71 (br m, 2H); MS (ESI): 581 [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 50% EtOAc:CH2Cl2)

Sources & evidence

ORD record
ord-e7ec42aef4494698b047838c2e6b1661
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

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