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

HRID 352602Notes

Reaction equation

HRID 352602 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-14ddb98e5cb449248fdde804cd4a6873
Source dataset
uspto-grants-2004_06
Patent number
US06747054B2

Reaction notes

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