Chloromethyl Methyl Ether → (R)-N-(1-(methoxymethoxy)-4-methylpentan-2-yl)-3,4-dimethylbenzamide

HRID 1644068

Reaction equation

[OH:1][CH2:2][C@H:3]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([CH3:17])[CH:11]=1)[CH2:4][CH:5]([CH3:7])[CH3:6].[OH-].[Na+].Cl[CH2:22][O:23][CH3:24]>CN(C=O)C>[CH3:22][O:23][CH2:24][O:1][CH2:2][C@H:3]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([CH3:17])[CH:11]=1)[CH2:4][CH:5]([CH3:7])[CH3:6]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (R)—N-(1-hydroxy-4-methylpentan-2-yl)-3,4-dimethylbenzamide (Example 71a) (0.24 mmol) dissolved in dry DMF (2 mL) was added at 0° C. powdered NaOH (0.36 mmol, 14.5 mg, 1.5 eq) and the mixture was stirred for 1 hr at 0° C. Then chloro-methoxy-methane (19.3 μl, 1 eq) was added and the reaction stirred at 0° C. for 1 hour. The reaction was quenched with water (30 mL) and the mixture was extracted with dichloromethane. The organic phase was dried over MgSO4 and evaporated. The crude product was purified by preparative TLC (20% ethyl acetate/hexanes) to give 37.7 mg of (R)—N-(1-(methoxymethoxy)-4-methylpentan-2-yl)-3,4-dimethylbenzamide (53%). 1H NMR (500 MHz, CDCl3): δ 0.98-1.00 (t, 6H), 1.49-1.53 (m, 1H), 1.58-1.64 (m, 1H), 1.69-1.73 (m, 2H), 2.32-2.33 (d, 6H), 3.38-3.39 (t, 3H), 3.64-3.72 (ddd, 2H), 4.41-4.44 (m, 1H), 4.65-4.69 (dd, 2H), 6.37-6.39 (d, 1H), 7.19-7.21 (d, 1H), 7.50-7.52 (dd, 1H), 7.60 (sb, 1H). MS (M+H, 294.3).

Workup

stirringthe reaction stirred at 0° C. for 1 hour
customThe reaction was quenched with water (30 mL)
extractionthe mixture was extracted with dichloromethane
dry with materialThe organic phase was dried over MgSO4
customevaporated
customThe crude product was purified by preparative TLC (20% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-f63d130e191247cb821713b16b4cff8d
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08124121B2

Linked notes

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