Aniline → (S)-2-(6-Chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxy-N-phenylbutanamide

HRID 2043191Notes

Reaction equation

HRID 2043191 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Al](C)C.CCCCCC.[Cl:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[N:25]([C@H:29]1[CH2:33][CH2:32][O:31][C:30]1=[O:34])[CH2:24][CH2:23][CH2:22]2>C(Cl)Cl>[Cl:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[N:25]([C@@H:29]([CH2:33][CH2:32][OH:31])[C:30]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:34])[CH2:24][CH2:23][CH2:22]2

Participants

6

Reactant 4

HCID 6115AnilineHCID 8058HexaneHCID 16682925TrimethylaluminumHCID 59465621(S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one

Product 1

HCID 59465889(S)-2-(6-Chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxy-N-phenylbutanamideYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Prepared using general procedure 60: To a solution of aniline (1.0 mL, 11.1 mmol) in CH2Cl2 (25 mL) under nitrogen at RT was added a solution of trimethylaluminum in hexane (2.0 M, 5.5 mL, 11.0 mmol) over 5 min. After stirring at RT for 20 min, a solution of (S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-dihydrofuran-2(3H)-one (2.32 g, 9.2 mmol) in CH2Cl2 (25 mL) was added over 10 min. Stirring was continued for 18 h at RT, then the reaction mixture was cooled to 0° C. and quenched by careful addition of aqueous 1M HCl (25 mL). Phases were separated, and the aqueous phase was extracted with CH2Cl2 (2×50 mL). The combined organic extracts were dried over MgSO4 and concentrated. Purification via silica gel chromatography using 2-10% MeOH in CH2Cl2 gave (S)-2-(6-Chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxy-N-phenylbutanamide as a white solid (2.56 g, 81%). 1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 7.60 (dd, J=1.0, 8.5 Hz, 2H), 7.29 (dd, J=1.8, 14.1 Hz, 2H), 7.07-6.95 (m, 3H), 6.80 (d, J=9.0 Hz, 1H), 4.67 (t, J=4.9 Hz, 1H), 4.56 (t, J=7.2 Hz, 1H), 3.47 (dd, J=6.1, 11.2 Hz, 2H), 3.39-3.34 (m, 1H), 3.31-3.25 (m, 1H), 2.71-2.68 (m, 2H), 2.15-2.04 (m, 1H), 1.94-1.80 (m, 3H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=345.3; tR=3.44 min.

Workup

  1. customPrepared
  2. stirringStirring
  3. waitwas continued for 18 h at RT
  4. temperaturethe reaction mixture was cooled to 0° C.
  5. customquenched by careful addition of aqueous 1M HCl (25 mL)
  6. customPhases were separated
  7. extractionthe aqueous phase was extracted with CH2Cl2 (2×50 mL)
  8. dry with materialThe combined organic extracts were dried over MgSO4
  9. concentrationconcentrated
  10. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-534043285d304e3e98d82729e3e4d6d2
Source dataset
uspto-grants-2013_11
Patent number
US08586589B2

Reaction notes

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