Triethylamine → HCID 117974455, compound

HRID 1776106Notes

Reaction equation

HRID 1776106 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].CCN(CC)CC.[CH:40]1([C:45](Cl)=[O:46])[CH2:44][CH2:43][CH2:42][CH2:41]1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH:40]1([C:45]([O:29][C@@H:15]2[C@@H:16]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[CH2:17][CH2:18][CH2:19][C@H:11]([N:7]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:32])[CH2:8][O:9][CH3:10])[C:12](=[O:31])[O:13][C@H:14]2[CH3:30])=[O:46])[CH2:44][CH2:43][CH2:42][CH2:41]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 78284Cyclopentanecarbonyl chlorideHCID 117974671HCID 117974671, compound

Product 1

HCID 117974455HCID 117974455, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 20 mL vial was charged with tert-butyl((3S,7R,8R,9S)-8-hydroxy-7-(4-methoxybenzyl)-9-methyl-2-oxooxonan-3-yl)(methoxymethyl)carbamate (200 mg, 0.443 mmol), CH2Cl2 (2215 μl), NEt3 (185 μl, 1.329 mmol) and DMAP (5.41 mg, 0.044 mmol). The reaction mixture was cooled to 0° C. in an ice bath under N2 and cyclopentanecarbonyl chloride (76 mg, 0.576 mmol) was added in one portion. The reaction became dark brownish-yellow. After stirring for 2 h, the reaction mixture was quenched by the addition of saturated aqueous NaHCO3. The mixture was extracted with CH2Cl2 (3×) and the combined organic layers were washed with brine, dried over MgSO4, concentrated, and purified by column chromatography on SiO2 (0→100% EtAOx/hexanes) to provide the title compound as a yellow solid (85 mg, 35.0%): 1H NMR (400 MHz, CDCl3) δ 7.01 (d, J=8.5 Hz, 4H), 6.81 (d, J=8.4 Hz, 4H), 5.06-4.85 (m, 3H), 4.77 (d, J=11.6 Hz, 1H), 4.57 (dd, J=10.7, 6.0 Hz, 0H), 4.29-4.17 (m, 1H), 3.78 (s, 3H), 3.38-3.26 (m, 3H), 2.74 (p, J=8.0 Hz, 1H), 2.61 (dd, J=13.7, 3.7 Hz, 1H), 2.31 (dd, J=13.7, 11.1 Hz, 1H), 2.20-2.07 (m, 1H), 1.99-1.52 (m, 8H), 1.51-1.40 (m, 9H), 1.27 (d, J=5.8 Hz, 3H), 1.15-0.96 (m, 1H), 0.97-0.87 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 176.26, 173.56, 157.94, 155.49, 131.94, 129.59, 113.80, 81.21, 75.54, 72.72, 58.52, 55.43, 55.22, 44.32, 44.04, 35.77, 30.09, 30.00, 29.58, 28.20, 26.48, 25.72, 25.70, 19.09, 17.56; ESIMS m/z 570.5 ([M+Na]+).

Workup

  1. customthe reaction mixture was quenched by the addition of saturated aqueous NaHCO3
  2. extractionThe mixture was extracted with CH2Cl2 (3×)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. custompurified by column chromatography on SiO2 (0→100% EtAOx/hexanes)

Sources & evidence

ORD record
ord-9057cf7d27b74e6ebee7b7d4ce886a1b
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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