N-[(E)-3-methylbutan-2-ylideneamino]-2,4,6-tri(propan-2-yl)benzenesulfonamide → (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)but-3-en-2-yl(4-methyl-3-methylene-2-oxopentyl)carbamate

HRID 627091Notes

Reaction equation

[CH:1]([C:4]1[CH:9]=C(C(C)C)C=C(C(C)C)[C:5]=1S(N/N=C(/C(C)C)\C)(=O)=O)(C)[CH3:2].C([Li])CCC.[Si:31]([O:38][CH2:39][C@@H:40]([N:43]([CH2:51][C:52](N(OC)C)=[O:53])[C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH:41]=[CH2:42])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>CCCCCC.CN(CCN(C)C)C>[Si:31]([O:38][CH2:39][C@@H:40]([N:43]([CH2:51][C:52](=[O:53])[C:1](=[CH2:2])[CH:4]([CH3:9])[CH3:5])[C:44](=[O:50])[O:45][C:46]([CH3:48])([CH3:49])[CH3:47])[CH:41]=[CH2:42])([C:34]([CH3:35])([CH3:36])[CH3:37])([CH3:32])[CH3:33]

Participants

Conditions

Temperature: -78 °C

Procedure

To a suspension of (E)-2,4,6-triisopropyl-N′-(3-methylbutan-2-ylidene)benzenesulfonohydrazide (Intermediate 33, 8 g, 21.82 mmol) in hexane (65 mL) and TMEDA (6.50 mL) at −78° C. was added dropwise n-butyllithium (1.6M in hexanes) (34.1 mL, 54.56 mmol). The reaction mixture turned orange and was stirred for 30 minutes at −78° C., then was warmed to 0° C. and bubbling started immediately. The suspension became a yellow solution. After ˜15 minutes the bubbling stopped and (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)but-3-en-2-yl(2-(methoxy(methyl)-amino)-2-oxoethyl)carbamate (Intermediate 5, 4.39 g, 10.91 mmol) was added as a solution in hexane (2 mL). After ˜15 minutes LC/MS shows desired product and no remaining Weinreb amide starting material. The reaction mixture was quenched with saturated sodium bicarbonate and extracted with ether twice. The ether extracts were dried over magnesium sulfate, filtered and concentrated to afford a yellow oil. Silica gel chromatography (0%-10% ethyl acetate/hexanes) afforded the desired product (2.219 g, 49.4%) as a light yellow oil.

Workup

temperaturewas warmed to 0° C.
custombubbling
waitAfter ˜15 minutes the bubbling stopped
waitAfter ˜15 minutes LC/MS shows

Sources & evidence

ORD record: ord-8be8cd70b3784a9d9f31083787d009c0
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309245B2

Reaction notes

Loading…