Sodium hydride → (S)-tert-butyl (4-cyano-2,3-dihydro-1H-inden-1-yl)(2-(dimethylamino)-2-oxoethyl)carbamate

HRID 1809512Notes

Reaction equation

[C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C@@H:7]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])#[N:2].[H-].[Na+].Cl[CH2:23][C:24]([N:26]([CH3:28])[CH3:27])=[O:25]>CN(C=O)C>[C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C@@H:7]2[N:12]([CH2:23][C:24]([N:26]([CH3:28])[CH3:27])=[O:25])[C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])#[N:2]

Participants

Conditions

Temperature: 0 °C

Procedure

Prepared using General Procedure 9. To a solution of (S)-tert-butyl 4-cyano-2,3-dihydro-1H-inden-1-ylcarbamate INT-9 (3.0 g, 1.16 mmol) in DMF (20 mL) was added NaH (1.39 g of 60% dispersion in mineral oil, 34.8 mmol) at 0° C. with stirring for 3 h before the addition of 2-chloro-N,N-dimethylacetamide (2.82 g, 23.2 mmol). The reaction mixture was stirred at 0° C. for 0.5 h and then warmed to room temperature for 1 h. The reaction mixture was quenched with water (3 mL) slowly at 0° C. The mixture was partitioned between EA (3×20 mL) and water (50 mL). The combined organic layers were concentrated and purified by chromatography (DCM/MeOH) to provide product 3.82 g (96.0%) of (S)-tert-butyl 4-cyano-2,3-dihydro-1H-inden-1-yl(2-(dimethylamino)-2-oxoethyl)carbamate as a light brown solid. LCMS-ESI (m/z) calculated for C19H25ClN6O6; 343.4; found 366.1 [M+Na]+, tR=3.16 min.

Workup

customPrepared
temperaturewarmed to room temperature for 1 h
customThe reaction mixture was quenched with water (3 mL) slowly at 0° C
customThe mixture was partitioned between EA (3×20 mL) and water (50 mL)
concentrationThe combined organic layers were concentrated
custompurified by chromatography (DCM/MeOH)

Sources & evidence

ORD record: ord-16789660562c4ea3b05e887c1b0d5349
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362048B2

Reaction notes

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