Sodium hydride → N-[6-Benzyloxy-2,2-dimethylchroman-4-yl]-N-(2-methoxyethyl)methanesulfonamide

HRID 567069Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[O:15][C:14]([CH3:20])([CH3:19])[CH2:13][CH:12]2[NH:21][S:22]([CH3:25])(=[O:24])=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:28][O:29][CH2:30][CH2:31]Br>CC(N(C)C)=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[O:15][C:14]([CH3:20])([CH3:19])[CH2:13][CH:12]2[N:21]([CH2:31][CH2:30][O:29][CH3:28])[S:22]([CH3:25])(=[O:23])=[O:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

8.9 g (25 mmol) of 6-benzyloxy-4-(methylsulfonyl)amino-2,2-dimethylchroman (Example 1e) were introduced in portions at 10° C. into a suspension of 0.54 g (30 mmol) of sodium hydride (60% dispersion) in 80 ml of DMA. After stirring at 50° C. for 30 min, 2.2 ml (22 mmol) of 2-methoxyethyl bromide were added dropwise at RT. The mixture was then heated to 110° C. for 1 h, concentrated in vac., the residue was treated with water and aqueous hydrochloric acid, the resinous product was taken up with EA, the solution was dried and concentrated, and the residue was chromatographed on silica gel using toluene/EA (3:1). 2.2 g of product were crystallized from appropriate fractions using petroleum ether, m.p. 66-68° C.

Workup

temperatureThe mixture was then heated to 110° C. for 1 h
concentrationconcentrated in vac
addition, the residue was treated with water and aqueous hydrochloric acid
customthe solution was dried
concentrationconcentrated
customthe residue was chromatographed on silica gel
custom2.2 g of product were crystallized from appropriate fractions

Sources & evidence

ORD record: ord-ba8e8cc963154c229a1b51b470afb90f
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06177449B1

Reaction notes

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