Methylamine → HCID 118377828, compound

HRID 1055523Notes

Reaction equation

HRID 1055523 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]1[CH2:52][O:51]1)[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:53][NH2:54]>CO.O1CCCC1>[CH3:53][NH:54][CH2:52][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)[OH:51]

Participants

4

Reactant 2

HCID 6329MethylamineHCID 118377953HCID 118377953, compound

Product 1

HCID 118377828HCID 118377828, compoundYield 71.6%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(oxiran-2-yl)-6,8-dioxabicyclo[3.2.1]octane 10a (50 mg, 0.56 mmol, obtained from the synthetic method described in step 1 of example 10) in a methanol/tetrahydrofuran mixture (v/v=2/1, 9 mL) was added methylamine solution (1 mL, 1.25 mmol). The mixture was heated to 55° C. and stirred for 16 h. The resulting mixture was extracted with ethyl acetate (20 mL×2). The combined organic layers were washed with water (10 mL×2) and saturated brine (10 mL×2) in turn, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with EtOAc to give the title compound 11a as a white solid (37.4 mg, 71.6%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.41 (m, 2H), 7.40 (m, 1H), 7.32 (m, 3H), 7.26 (m, 6H), 7.17 (m, 3H), 7.04 (d, 2H), 6.85 (m, 2H), 6.73 (m, 2H), 4.87 (m, 1H), 4.75 (m, 3H), 4.26 (m, 1H), 4.11 (m, 2H), 3.97 (m, 2H), 3.92 (m, 3H), 3.82 (m, 2H), 3.72 (m, 3H), 2.65 (m, 1H), 2.55 (m, 1H), 2.22 (s, 3H), 1.27 (t, 3H).

Workup

  1. extractionThe resulting mixture was extracted with ethyl acetate (20 mL×2)
  2. washThe combined organic layers were washed with water (10 mL×2) and saturated brine (10 mL×2) in turn
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by silica gel chromatography
  7. washeluted with EtOAc

Sources & evidence

ORD record
ord-0cd6ad41f9d543f6b42c7b3caa8f49e0
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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