Sodium hydride → (S)-1-{(S)-2-[(S)-2-tert-Butoxycarbonylamino-3-(4-methoxy-phenyl)-propionylamino]-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid but-3-enyl ester

HRID 1427787Notes

Reaction equation

HRID 1427787 reaction equation
[H-].[Na+].Cl[C:4](Cl)(Cl)[CH2:5][O:6][C:7]([C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15](=[O:53])[C@@H:16]([NH:32][C:33](=[O:52])[C@@H:34]([NH:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH:19]=2)[NH:10]1)=[O:8].[CH2:56](O)[CH2:57]C=C>O1CCCC1>[CH2:5]([O:6][C:7]([C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15](=[O:53])[C@@H:16]([NH:32][C:33](=[O:52])[C@@H:34]([NH:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH:19]=2)[NH:10]1)=[O:8])[CH2:4][CH:56]=[CH2:57]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 693893-Buten-1-olHCID 71225414HCID 71225414, compound

Product 1

HCID 86675868(S)-1-{(S)-2-[(S)-2-tert-Butoxycarbonylamino-3-(4-methoxy-phenyl)-propionylamino]-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid but-3-enyl esterYield 84.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydride (6 mg, 0.139 mmol) was added to a solution of (S)-1-{(S)-2-[(S)-2-tert-butoxycarbonylamino-3-(4-methoxy-phenyl)-propionylamino]-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (570 mg, 0.698 mmol) and 3-buten-1-ol (601 μL, 6.98 mmol) in tetrahydrofuran (10 mL) and the reaction stirred at 50° C. under nitrogen for 18 h. The reaction was cooled and the mixture passed through a plug of silica gel (eluting twice with ethyl acetate, 50 mL) to afford the title compound (438 mg, 85%) as a colourless oil (438 mg, 85%). 1H NMR (300 MHz, CDCl3) δ0.20 (s, 6H), 1.00 (s, 9H), 1.10-140 (m, 2H), 1.40 (s, 9H), 1.72-1.86 (m, 2H), 2.33-2.46 (m, 3H), 2.60-3.05 (m, 5H), 3.50 (d, 11.4 Hz, 1H), 3.80 (s, 3H), 4.15-4.35 (m, 4H), 4.95 (br s, 1H), 5.09-5.19 (m, 2H), 5.60-5.70 (m, 1H), 5.71-5.87 (m, 1H), 6.42 (d, J=8.0 Hz, 1H), 6.62-6.80 (m, 3H), 6.82 (d, J=8.7 Hz, 2H), 7.07-7.16 (m, 3H). LCMS (m/z) 739.40 [M+H], Tr=5.82 min.

Workup

  1. temperatureThe reaction was cooled
  2. washeluting twice with ethyl acetate, 50 mL)

Sources & evidence

ORD record
ord-0e7d3071cb9d47ad91bfa0d59e7d21e5
Source dataset
uspto-grants-2015_01
Patent number
US08933015B2

Reaction notes

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