Ammonium Chloride → 1'-(benzyl)-spiro[isobenzofuran-1(3H),4'-piperidin]-3-thione

HRID 587645Notes

Reaction equation

[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][C:11]3([C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:15](=O)[O:14]3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:32]2)=CC=1.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[CH2:7]([N:8]1[CH2:13][CH2:12][C:11]2([C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[S:32])[O:14]2)[CH2:10][CH2:9]1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a mixture of 1′-(phenylmethyl)-spiro[isobenzofuran-1(3H),4′-piperidin]-3-one (25 g, 85.2 mmol) [C.A.S. 37663-42-6] in toluene (600 ml), was added 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide (Lawesson's reagent) (34.47 g, 85.2 mmol was added. The reaction mixture was heated at 140° C. for 2 h. After cooling, the mixture was poured into NH4Cl (aqueous sat. solution) and extracted with DCM. The organic phase was separated, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (silica gel; DCM/MeOH 3% as eluent). The desired fractions were collected and concentrated in vacuo to a residue that was purified by HPLC to yield intermediate D72 (8 g, 30.3%).

Workup

additionwas added
temperatureAfter cooling
extractionextracted with DCM
customThe organic phase was separated
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (silica gel; DCM/MeOH 3% as eluent)
customThe desired fractions were collected
concentrationconcentrated in vacuo to a residue that
customwas purified by HPLC
customto yield intermediate D72 (8 g, 30.3%)

Sources & evidence

ORD record: ord-10381f41c8724e6e96622a5b93b27e10
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09226930B2

Reaction notes

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