Butyn-2-one → HCID 117974638, compound

HRID 1776105Notes

Reaction equation

HRID 1776105 reaction equation
[C:1]([O:5][C:6](=[O:32])[N:7]([C@H:11]1[CH2:19][CH2:18][CH2:17][C@H:16]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C@@H:15]([OH:29])[C@H:14]([CH3:30])[O:13][C:12]1=[O:31])[CH2:8][O:9][CH3:10])([CH3:4])([CH3:3])[CH3:2].[CH3:33][C:34](=[O:37])[C:35]#[CH:36]>C(Cl)Cl.C1N2CCN(CC2)C1>[C:1]([O:5][C:6](=[O:32])[N:7]([C@H:11]1[CH2:19][CH2:18][CH2:17][C@H:16]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C@@H:15]([O:29][CH:36]=[CH:35][C:34](=[O:37])[CH3:33])[C@H:14]([CH3:30])[O:13][C:12]1=[O:31])[CH2:8][O:9][CH3:10])([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 15018Butyn-2-oneHCID 117974671HCID 117974671, compound

Product 1

HCID 117974638HCID 117974638, compoundYield 55.8%

Reagents, catalysts & solvents 2

HCID 9237DabcoCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A round bottomed flask was charged with tert-butyl((3S,7R,8R,9S)-8-hydroxy-7-(4-methoxybenzyl)-9-methyl-2-oxooxonan-3-yl)(methoxymethyl)carbamate (400 mg, 0.886 mmol) in CH2Cl2 (4429 μl). To the solution was added DABCO (4.97 mg, 0.044 mmol) and the reaction mixture was cooled to 0° C. under N2. Upon addition of but-3-yn-2-one (83 μl, 1.063 mmol), the colorless solution became dark brown-orange. After stirring for 2 h, the reaction mixture was concentrated and purified directly by column chromatography on SiO2 (0→10%, hold, 10→20%, hold, 20→50% hold EtOAc/hexanes gradient) to afford the title compound as a thick colorless oil (257 mg, 55.8%): 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J=12.2 Hz, 1H), 7.03 (d, J=8.6 Hz, 2H), 6.81 (d, J=8.6 Hz, 2H), 5.75 (d, J=12.4 Hz, 1H), 5.06-4.85 (m, 2H), 4.82-4.73 (m, 1H), 4.61-4.50 (m, 1H), 4.26-4.14 (m, 1H), 3.78 (s, 3H), 3.37-3.26 (m, 3H), 2.82 (dd, J=13.6, 4.0 Hz, 1H), 2.41-2.28 (m, 1H), 2.24-2.01 (m, 1H), 2.18 (s, 3H), 1.62-1.39 (m, 12H), 1.34 (d, J=6.4 Hz, 3H), 1.26 (t, J=7.1 Hz, 2H), 0.92 (dt, J=13.6, 4.6 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 197.24, 173.18, 163.24, 158.03, 155.34, 131.19, 129.61, 113.83, 108.08, 88.73, 88.61, 81.19, 76.86, 76.23, 75.39, 72.61, 72.49, 58.42, 56.97, 55.41, 55.14, 44.87, 35.82, 30.38, 29.45, 28.43, 28.27, 28.16, 26.38, 26.18, 19.16, 18.24; ESIMS m/z 542.4 ([M+Na)]+).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. custompurified directly by column chromatography on SiO2 (0→10%, hold, 10→20%, hold, 20→50% hold EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-4a57dc6865ec42b79ee57af71e6e462c
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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