Diisopropylethylamine → 2-((R)-5-Bromoindan-2-yl)-6-[(S)-1-(tetrahydrofuran-2-yl)methoxy]-3,4-dihydro-2H-isoquinolin-1-one

HRID 1039642Notes

Reaction equation

HRID 1039642 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@@H:6]([NH2:11])[CH2:5]2.C(N(C(C)C)CC)(C)C.Cl[CH2:22][CH2:23][C:24]1[CH:32]=[C:31]([O:33][CH2:34][C@@H:35]2[CH2:39][CH2:38][CH2:37][O:36]2)[CH:30]=[CH:29][C:25]=1[C:26](Cl)=[O:27].CC(C)([O-])C.[K+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@@H:6]([N:11]1[CH2:22][CH2:23][C:24]3[C:25](=[CH:29][CH:30]=[C:31]([O:33][CH2:34][C@@H:35]4[CH2:39][CH2:38][CH2:37][O:36]4)[CH:32]=3)[C:26]1=[O:27])[CH2:5]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 112758701H-Inden-2-amine, 5-bromo-2,3-dihydro-, (2R)-HCID 23665647Potassium tert-butoxideHCID 867620992-(2-chloroethyl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzoyl chloride

Product 1

HCID 666798112-((R)-5-Bromoindan-2-yl)-6-[(S)-1-(tetrahydrofuran-2-yl)methoxy]-3,4-dihydro-2H-isoquinolin-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (R)-5-bromoindan-2-ylamine (hydrochloride, 1.05 g), THF (20 ml) and diisopropylethylamine (1.0 g) was admixed with 2-(2-chloroethyl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzoyl chloride (1.28 g; from 6-[(S)-1-(tetrahydrofuran-2-yl)methoxy]-isochroman-1-one by boiling with thionyl chloride). After 5 minutes, potassium tert-butoxide (1.42 g) was added. After 12 hours, the reaction mixture was partitioned between water and ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was chromatographed on silica gel (eluent: 1:1 ethyl acetate/heptane). This afforded the product with the molecular weight of 442.36 (C23H24BrNO3); MS (ESI): 442 (M+H+).

Workup

  1. waitAfter 12 hours
  2. customthe reaction mixture was partitioned between water and ethyl acetate
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel (eluent: 1:1 ethyl acetate/heptane)
  6. customThis afforded the product with the molecular weight of 442.36 (C23H24BrNO3)

Sources & evidence

ORD record
ord-e2c693cc188047798955e132ec9ab5c9
Source dataset
uspto-grants-2013_10
Patent number
US08552199B2

Reaction notes

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