Trimethylaluminum → HCID 70654405, compound

HRID 2178203Notes

Reaction equation

[NH2:1][C@@:2]([C@H:11]1[CH2:15][O:14][CH2:13][C@@H:12]1[S:16][CH2:17][C:18]#[N:19])([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[F:10])[CH3:3].C[Al](C)C>C1(C)C=CC=CC=1>[F:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[C@:2]1([CH3:3])[C@@H:11]2[C@H:12]([CH2:13][O:14][CH2:15]2)[S:16][CH2:17][C:18]([NH2:19])=[N:1]1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of the {rel-(3R,4S)-4-[(S)-1-amino-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ylsulfanyl}-acetonitrile (460 mg, 1.64 mmol) in toluene (6 ml) was treated dropwise with trimethylaluminum (902 μl, 1.8 mmol) at room temperature. The reaction mixture was stirred at 60° C. for 2 hours, thereafter, extracted with a mixture of a saturated solution of sodium hydrogencarbonate and ethyl acetate. The combined organic layers were dried over sodium sulphate and evaporated at reduced pressure. The residue was purified by flash chromatography on silica gel using a mixture of ethyl acetate, methanol, ammonium hydroxide=100:10:1 as the eluent. The (3aR,8S,8aS)-rel-8-(2-fluoro-phenyl)-8-methyl-1,3,3a,5,8,8a-hexahydro-2-oxa-4-thia-7-aza-azulen-6-ylamine (200 mg, 43% yield) was obtained as a light yellow oil. MS (ISP): m/z=281.0 [M+H]+.

Workup

extractionextracted with a mixture of a saturated solution of sodium hydrogencarbonate and ethyl acetate
dry with materialThe combined organic layers were dried over sodium sulphate
customevaporated at reduced pressure
customThe residue was purified by flash chromatography on silica gel using
additiona mixture of ethyl acetate, methanol, ammonium hydroxide=100:10:1 as the eluent

Sources & evidence

ORD record: ord-523d473c85b047c887844f800788e8d0
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067924B2

Reaction notes

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