Benzyl mercaptan → Tert-butyl 5-(benzylthio)isoindoline-2-carboxylate

HRID 331056Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]2.CCN(C(C)C)C(C)C.[CH2:27]([SH:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:27]([S:34][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]2)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of tert-butyl 5-bromoisoindoline-2-carboxylate (2 g, 6.71 mmol) in 1,4-dioxane (17.1 mL) in a round bottom flask was added Pd2(dba)3 (0.154 g, 0.168 mmol), xantphos (0.194 g, 0.335 mmol), DIPEA (2.343 mL, 13.41 mmol) and benzyl mercaptan (0.873 mL, 7.38 mmol) and the resulting mixture was stirred and heated at 90° C. under nitrogen for overnight. The reaction mixture was filtered through celite, rinsed with ethyl acetate and the filtrate concentrated in vacuo. The residue was purified on silica gel, eluting with ethyl acetate in cyclohexane (0-20%) to afford the title compound (2.11 g). LCMS (A): m/z [(M-tBu)+H]+ 286, C20H23NO2S requires 341 (acidic).

Workup

filtrationThe reaction mixture was filtered through celite
washrinsed with ethyl acetate
concentrationthe filtrate concentrated in vacuo
customThe residue was purified on silica gel
washeluting with ethyl acetate in cyclohexane (0-20%)

Sources & evidence

ORD record: ord-de68a815ca0d40138c863b253ac97dce
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877742B2

Reaction notes

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