Chloromethyl Methyl Ether → HCID 57504916, compound

HRID 2060789Notes

Reaction equation

HRID 2060789 reaction equation
[OH:1][C@H:2]1[CH2:19][C@:5]2([C:20]3[CH:21]=[C:22]([C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=4)[CH:23]=[CH:24][CH:25]=3)[N:6]=[C:7]([NH:10][C:11](=[O:18])[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[S:8][CH2:9][C@@H:4]2[CH2:3]1.Cl[CH2:35][O:36][CH3:37].C(N(C(C)C)CC)(C)C>ClCCl>[CH3:33][O:32][C:28]1[CH:27]=[C:26]([C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([C@:5]34[CH2:19][C@H:2]([O:1][CH2:35][O:36][CH3:37])[CH2:3][C@H:4]3[CH2:9][S:8][C:7]([NH:10][C:11](=[O:18])[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[N:6]4)[CH:21]=2)[CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 57504914HCID 57504914, compound

Product 1

HCID 57504916HCID 57504916, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred 0° C. solution of N-((4aR,6R,7aS)-6-hydroxy-7a-(3′-methoxybiphenyl-3-yl)-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-yl)benzamide (0.087 g, 0.190 mmol) in anhydrous dichloromethane (0.6 mL) is added chloromethoxymethane (0.031 g, 0.379 mmol), followed by diisopropylethylamine (0.049 g, 0.379 mmol). The resulting mixture is stirred at 0° C. for 1 hour, and then is warmed to room temperature over 24 h. The mixture is diluted with dichloromethane, quenched by addition of saturated aqueous solution of sodium bicarbonate, and is extracted three times with dichloromethane. The combined organic layers are washed with water and brine. The organic layer is dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product is purified by silica gel chromatography eluting with a linear gradient of 0% to 60% ethyl acetate in hexanes over 26 minutes to give the title compound (0.089, 93%). ES/MS m/e: 503 (M+1).

Workup

  1. temperatureis warmed to room temperature over 24 h
  2. customquenched by addition of saturated aqueous solution of sodium bicarbonate
  3. extractionis extracted three times with dichloromethane
  4. washThe combined organic layers are washed with water and brine
  5. dry with materialThe organic layer is dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product is purified by silica gel chromatography
  9. washeluting with a linear gradient of 0% to 60% ethyl acetate in hexanes over 26 minutes

Sources & evidence

ORD record
ord-0ea68af3cf2244bcb50a65d0e103b62a
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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