Water → HCID 58707335, compound

HRID 1910617Notes

Reaction equation

HRID 1910617 reaction equation
[CH3:1][CH:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]1[NH2:12].F[C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[S:21]([CH3:24])(=[O:23])=[O:22].C(N(C(C)C)CC)(C)C.O>CN(C)C=O>[F:20][C:18]1[CH:19]=[CH:14][C:15]([S:21]([CH3:24])(=[O:23])=[O:22])=[C:16]([NH:12][CH:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[CH2:10][CH2:11][CH:2]2[CH3:1])[CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27583362,4-Difluoro-1-(methylsulfonyl)benzeneHCID 143486522-Methyl-1,2,3,4-tetrahydronaphthalen-1-amine

Product 1

HCID 58707335HCID 58707335, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3,4-Dihydro-2-methylnaphthalen-1(2H)-one (5.2 g, 33.0 mmol), titanium(IV) isopropoxide (19.3 mL, 66.0 mmol) and 2 M solution of ammonia in ethanol (82.0 mL, 165 mmol) were stirred at room temperature for 6 h. The reaction was cooled to 0° C. and sodium borohydride was added portionwise during 10 min. (1.87 g, 49.5 mmol); the resultant mixture was stirred at rt for an additional 3 h. The reaction was quenched by pouring it into ammonium hydroxide (2 M, 20 mL), the precipitate that formed was filtered off and washed with ethyl acetate (20 mL×3). The organic layer was separated and the remaining aqueous layer was extracted with ethyl acetate (20 mL×2). The combined organic extracts were washed with 1 M HCl (15 mL). The acidic aqueous extracts were washed with ethyl acetate (30 mL), then treated with aqueous sodium hydroxide (2 M) to pH 10-12, and extracted with ethyl acetate (20 mL×3). The combined organic extracts were washed with brine (15 mL), dried (Na2SO4), and concentrated in vacuo to afford the desired product (1.20 g, 22.6% yield). The compound was used without further purification for the following reaction. A solution of 1,2,3,4-tetrahydro-2-methylnaphthalen-1-amine (63.0 mg, 0.39 mmol), 2,4-difluoro-1-(methylsulfonyl)benzene (85.0 mg, 0.43 mmol) and diisopropylethylamine (200 mg, 1.56 mmol) in N,N-dimethylformamide (1 mL) was stirred at 110° C. for 16 h. The reaction was cooled to room temperature, poured over water and extracted with diethyl ether. The solvent was concentrated in vacuo and the residue was purified by silica chromatography (10% ethyl acetate in hexanes) to give 65.0 mg (50%) of the desired product. 1H NMR (400 MHz, CDCl3) δ 7.79 (dd, 1H), 7.20 (m, 4H), 6.52 (m, 3H), 4.25 (t, 1H), 2.99 (s, 3H), 2.86 (t, 1H), 2.65-1.65 (m, 4H), 1.16 (d, 3H); MS (ESI) m/z: 333.6 (M++1).

Workup

  1. customThe compound was used without further purification for the following reaction
  2. extractionextracted with diethyl ether
  3. concentrationThe solvent was concentrated in vacuo
  4. customthe residue was purified by silica chromatography (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-87262a7a08ba4726ac269ba892a80249
Source dataset
uspto-grants-2013_12
Patent number
US08604021B2

Reaction notes

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