4-(3-Bromopropyl)benzonitrile → 4-(3-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzonitrile

HRID 458991Notes

Reaction equation

HRID 458991 reaction equation
[C:1]([Si:5]([CH3:24])([CH3:23])[O:6][CH:7]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:8][CH2:9][CH:10]1[NH:14][C:13](=[O:15])[CH2:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:36][CH2:37][CH2:38][C:39]1[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[CH:41][CH:40]=1>>[C:1]([Si:5]([CH3:24])([CH3:23])[O:6][CH:7]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:8][CH2:9][CH:10]1[CH2:11][CH2:12][C:13](=[O:15])[N:14]1[CH2:36][CH2:37][CH2:38][C:39]1[CH:40]=[CH:41][C:42]([C:43]#[N:44])=[CH:45][CH:46]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 3

HCID 4583644-(3-Bromopropyl)benzonitrileHCID 2724254Sodium bis(trimethylsilyl)amideHCID 129700855-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-one

Product 1

HCID 227124384-(3-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzonitrileYield 69.4%

Procedure

Analogous to the procedure described for Example 1A, Step D, the anion derived from 5-[3-(tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-one (262.8 mg, 0.756 mmol) and NaHMDS (0.83 mL, 0.83 mmol) was reacted with 4-(3-bromo-propyl)-benzonitrile (186 mg, 0.832 mmol) at 70° C. for 24 h. Purification by medium pressure chromatography (5:1 hexanes:EtOAc to 1:1 hexanes:EtOAc to 1% MeOH in CH2Cl2 to 5% MeOH in CH2Cl2) provided 4-(3-{2-[3-(tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzonitrile (257.6 mg). 1H NMR (CDCl3) δ7.56 (m, 2H), 7.26 (m, 5H), 7.13 (m, 2H), 3.85 (m, 1H), 3.62 (m, 1H), 3.48 (m, 1H), 2.93 (m, 1H), 2.82–2.60 (m, 4H), 2.29 (m, 2H), 1.88–1.25 (m, 7H); MS 491.5 (M+1).

Workup

  1. customPurification by medium pressure chromatography (5:1 hexanes:EtOAc to 1:1 hexanes:EtOAc to 1% MeOH in CH2Cl2 to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-a3224c96f6cd404490ff7ca16635ee75
Source dataset
uspto-grants-2007_03
Patent number
US07192979B2

Reaction notes

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