Triethylamine → HCID 118377824, compound

HRID 1055524Notes

Reaction equation

HRID 1055524 reaction equation
[CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:50]([OH:52])[CH3:51])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:54]([O:56][CH2:57][CH3:58])=[O:55].C(N(CC)CC)C>ClCCl>[C:54](=[O:55])([O:52][CH:50]([C@:10]12[O:32][C@:13]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:42]=[CH:43][C:44]([O:47][CH2:48][CH3:49])=[CH:45][CH:46]=4)[CH:34]=3)([O:12][CH2:11]1)[C@H:14]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@@H:15]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C@@H:9]2[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:51])[O:56][CH2:57][CH3:58]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 118377829HCID 118377829, compound

Product 1

HCID 118377824HCID 118377824, compoundYield 33.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol 1m (0.2 g, 0.28 mmol, obtained from the synthetic method described in step 11 of example 1) in dichloromethane (20 mL) were added ethyl chloroformate (0.26 mL, 2.8 mmol), triethylamine (0.78 mL, 5.60 mmol) and 4-dimethyl aminopyridine (cat. 5 mg) in turn at room temperature. The mixture was heated to 30° C. and stirred for 16 hours. The resulting mixture was quenched with 20 mL of saturated ammonium chloride, and then extracted with dichloromethane (40 mL×2). The combined organic layers were washed with saturated brine (20 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=15/1 to give the title compound 12a as a light yellow solid (73.6 mg, 33.5%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.44 (s, 1H), 7.39-7.29 (m, 10H), 7.22 (dd, 5H), 7.08 (d, 2H), 6.91 (d, 2H), 6.77 (d, 2H), 5.10 (m, 1H), 4.97 (d, 1H), 4.90 (s, 1H), 4.81 (d, 2H), 4.33 (s, 1H), 4.21 (s, 1H), 4.20-4.09 (m, 2H), 4.07 (s, 1H), 4.04 (d, 2H), 4.00-3.92 (m, 3H), 3.86-3.76 (m, 2H), 3.66 (d, 1H), 1.41 (t, 3H), 1.29 (m, 6H).

Workup

  1. customThe resulting mixture was quenched with 20 mL of saturated ammonium chloride
  2. extractionextracted with dichloromethane (40 mL×2)
  3. washThe combined organic layers were washed with saturated brine (20 mL×2)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by silica gel chromatography
  8. washeluted with PE/EtOAc(v/v)=15/1

Sources & evidence

ORD record
ord-25a4945a9b6a44489450de83a74e9d83
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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