tert-Butyl 4-((1-(6-chloro-2-oxo-1,3-bis((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)vinyloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate → tert-Butyl 4-((1-(6-chloro-2-oxo-1,3-bis((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913940Notes

Reaction equation

HRID 913940 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:28]([O:30][CH2:31][C:32]2([C:45]3[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=3)[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]2)=[CH2:29])[C:5]2[N:9]([CH2:10][O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])[C:8](=[O:18])[N:7]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:6]=2[CH:27]=1>ClCCCl.[B-](F)(F)(F)F.CC[C@H]1P(C2C(P3[C@H](CC)CC[C@H]3CC)=CC=CC=2)[C@H](CC)CC1.C1[CH][CH]CC[CH][CH]C1.[Rh]>[Cl:1][C:2]1[CH:3]=[C:4]([CH:28]([O:30][CH2:31][C:32]2([C:45]3[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=3)[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:43])([CH3:44])[CH3:42])=[O:39])[CH2:34][CH2:33]2)[CH3:29])[C:5]2[N:9]([CH2:10][O:11][CH2:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])[C:8](=[O:18])[N:7]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:25])([CH3:26])[CH3:24])[C:6]=2[CH:27]=1

Participants

4

Reactant 1

HCID 57545986tert-Butyl 4-((1-(6-chloro-2-oxo-1,3-bis((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)vinyloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 57546037tert-Butyl 4-((1-(6-chloro-2-oxo-1,3-bis((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11549211CID 11549211CatalystHCID 111,2-DichloroethaneSolvent

Procedure

A solution of tert-butyl 4-((1-(6-chloro-2-oxo-1,3-bis((2-(trimethylsilyl)ethoxy)methyl)-2,3-dihydro-1H-benzo[d]imidazol-4-yl)vinyloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (470 mg, 0.616 mmol) in 1,2-dichloroethane (20 mL) was degassed by passing a stream of nitrogen through the solution for 1 h. The reaction was quickly treated with (−)-1,2-Bis((2R,5R)-2,5-diethylphospholano)benzene(cyclooctadiene)rhodium(1)tetrafluoroborate (50 mg, 0.076 mmol) and flushed with nitrogen for 10 minutes longer. The vessel was pressurized to 60 psi of hydrogen and shaken for 24 h. The mixture was concentrated and the crude mixture purified by column chromatography (8%→25% ethyl acetate/n-hexane) to give 420 mg (89%) as a foam semi-solid. 1H-NMR (CDCl3, 500 MHz) δ 7.21 (dd, 8.9, 5.2 Hz, 2H), 7.02 (d, J=1.8 Hz, 1H), 6.98 (dd, J=8.9, 8.6 Hz, 2H), 6.78 (d, J=2.1 Hz, 1H), 5.35 (d, J=11.6 Hz, 1H), 5.23 (m, 2H), 5.03 (d, J=11.6 Hz, 1H), 4.94 (q, J=6.4 Hz, 1H), 3.69 (m, 2H), 3.57 (t, J=8.1 Hz, 2H), 3.51 (m, 2H), 3.18 (m, 2H), 3.01 (m, 2H), 2.07 (m, 2H), 1.84 (m, 2H), 1.42 (s, 9H), 1.34 (d, J=6.7 Hz, 3H), 0.70-0.97 (m, 4H), −0.05 (s, 9H), −0.06 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 161.4 (d, J=246 Hz), 155.0, 154.8, 138.6, 130.3, 128.7 (d, J=7.7 Hz), 128.5, 128.3, 124.5, 120.0, 115.1 (d, J=21 Hz), 108.3, 79.4, 76.8, 71.5, 71.4, 70.9, 66.5, 66.0, 41.1, 40.2, 40.1, 32.2, 32.0, 28.6, 23.3, 18.0, 17.9, −1.4. Mass spec.: 786.01 (MNa)+.

Workup

  1. customfor 1 h
  2. customflushed with nitrogen for 10 minutes longer
  3. concentrationThe mixture was concentrated
  4. customthe crude mixture purified by column chromatography (8%→25% ethyl acetate/n-hexane)
  5. customto give 420 mg (89%) as a foam semi-solid

Sources & evidence

ORD record
ord-a68627e5f2ad42958bd5ff670d72a840
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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