Diisopropylethylamine → 5-(2,6-Dimethoxyphenyl)-1-(3-(2-methylthiazol-4-yl)benzyl)pyrrolidin-2-one

HRID 594387Notes

Reaction equation

HRID 594387 reaction equation
[NH2:1][CH:2]([C:9]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:10]=1[O:17][CH3:18])[CH2:3][CH2:4][C:5]([O:7]C)=O.CCN(C(C)C)C(C)C.[CH3:28][C:29]1[S:30][CH:31]=[C:32]([C:34]2[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=2)[CH:37]=O)[N:33]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.C(Cl)Cl>[CH3:18][O:17][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([O:15][CH3:16])[C:9]=1[CH:2]1[N:1]([CH2:37][C:36]2[CH:39]=[CH:40][CH:41]=[C:34]([C:32]3[N:33]=[C:29]([CH3:28])[S:30][CH:31]=3)[CH:35]=2)[C:5](=[O:7])[CH2:4][CH2:3]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 71277823-(2-Methyl-1,3-thiazol-4-yl)benzaldehydeHCID 69082397Methyl 4-amino-4-(2,6-dimethoxyphenyl)butanoate

Product 1

HCID 690827085-(2,6-Dimethoxyphenyl)-1-(3-(2-methylthiazol-4-yl)benzyl)pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of the chlorhydrate salt of methyl 4-amino-4-(2,6-dimethoxyphenyl)butanoate (100 mg; 0.34 mmol; 1.0 equiv.) in anh. DCE (1.5 ml) was treated successively with DIPEA (0.12 ml; 0.69 mmol; 2.0 equiv.), 3-(2-methylthiazol-4-yl)benzaldehyde (70 mg; 0.34 mmol; 1.0 equiv.), and NaBH(OAc)3 (102 mg; 0.48 mmol; 1.4 equiv.). The resulting mixture was further stirred at rt, under nitrogen, for 72 h. DCM (50 ml) and a solution of aq. sat. NaHCO3 (35 ml) were then added. The organic layer was further washed with a solution of aq. sat. NaHCO3 (35 ml) and with brine (35 ml). The resulting organic layer was then dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by preparative HPLC afforded 5-(2,6-dimethoxyphenyl)-1-(3-(2-methylthiazol-4-yl)benzyl)pyrrolidin-2-one as a beige solid. LC-MS (conditions A): tR=0.81 min.; [M+H]+: 409.15 g/mol.

Workup

  1. washThe organic layer was further washed with a solution of aq. sat. NaHCO3 (35 ml) and with brine (35 ml)
  2. dry with materialThe resulting organic layer was then dried over anh. MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness under reduced pressure
  5. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-7dec92a7c99f4960b21cce724dc6f693
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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