Water → HCID 90387899, compound

HRID 2201736Notes

Reaction equation

HRID 2201736 reaction equation
[CH3:1][C@@:2]12[C:18](=[O:19])[CH2:17][CH2:16][C@H:15]1[CH2:14][C@@H:13]1[C@H:4]([CH2:5][CH2:6][C@H:7]3[C@@:12]1([CH3:20])[CH2:11][CH2:10][C@H:9]([OH:21])[CH2:8]3)[CH2:3]2.CCN(C(C)C)C(C)C.[CH3:31][O:32][CH2:33]Cl.O>ClCCl.CN(C1C=CN=CC=1)C>[CH3:1][C@@:2]12[C:18](=[O:19])[CH2:17][CH2:16][C@H:15]1[CH2:14][C@@H:13]1[C@H:4]([CH2:5][CH2:6][C@H:7]3[C@@:12]1([CH3:20])[CH2:11][CH2:10][C@H:9]([O:21][CH2:31][O:32][CH3:33])[CH2:8]3)[CH2:3]2

Participants

7

Reactant 4

HCID 962WaterHCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 78323392HCID 78323392, compound

Product 1

HCID 90387899HCID 90387899, compoundYield 100.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 22 (120 mg, 0.41 mmol) in dried dichloromethane (15 mL) was added DIPEA (130 mg, 1.0 mmol), chloromethyl methyl ether (121 mg, 1.5 mmol), and DMAP (10 mg) at room temperature. After 16 h, water was added and the product extracted into dichloromethane (100 mL×2). The combined extracts were dried, filtered, and removed. The residue was purified by flash column chromatography (silica gel eluted with 10% EtOAc in hexanes) to afford compound 24 (138 mg, 100%): 1H NMR (CDCl3) δ 4.60 (s, 2H), 3.79-3.78 (m, 1H), 3.31 (s, 3H), 0.80 (s, 3H), 0.76 (s, 3H); 13C NMR (CDCl3) δ 220.9, 94.4, 71.5, 55.0, 54.5, 47.7, 45.8, 39.8, 39.6, 36.1, 35.6, 34.7, 33.4, 32.6, 31.7, 28.7, 26.2, 24.1, 23.9, 13.5, 11.3.

Workup

  1. extractionthe product extracted into dichloromethane (100 mL×2)
  2. customThe combined extracts were dried
  3. filtrationfiltered
  4. customremoved
  5. customThe residue was purified by flash column chromatography (silica gel eluted with 10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d2c8fe8d351843a2a7c624f2932052aa
Source dataset
uspto-grants-2016_06
Patent number
US09365502B2

Reaction notes

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