Toluene → (S)-3-(Hydroxymethyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 588729Notes

Reaction equation

[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1.[O:18]=[C:19]1[NH:27][C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[C@@:20]21[CH2:39][C:30]1=[N:31][CH:32]=[C:33]([C:35](OC)=[O:36])[CH:34]=[C:29]1[CH2:28]2>C1COCC1>[OH:36][CH2:35][C:33]1[CH:34]=[C:29]2[CH2:28][C@@:20]3([C:21]4[C:22](=[N:23][CH:24]=[CH:25][CH:26]=4)[NH:27][C:19]3=[O:18])[CH2:39][C:30]2=[N:31][CH:32]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of diisobutylaluminum hydride (DIBAL) in toluene (1 M, 2.2 mL, 2.2 mmol) was added dropwise to a solution of methyl (6S)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylate (described in Intermediate 5) (0.184 g, 0.62 mmols) in anhydrous THF at 0° C. The resulting mixture was stirred for 1 h at 0° C., then gradually warmed to ambient temperature and stirred for an additional 1 h. Excess DIBAL was quenched with ice and the mixture was partitioned between water and EtOAc (4×20 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with 5% MeOH in chloroform, to afford the title compound. MS: m/z=268.0 (M+1).

Workup

temperaturegradually warmed to ambient temperature
stirringstirred for an additional 1 h
customExcess DIBAL was quenched with ice
customthe mixture was partitioned between water and EtOAc (4×20 mL)
washThe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel
washeluting with 5% MeOH in chloroform

Sources & evidence

ORD record: ord-9683e932af4a4905b4ff9993a98ddb2a
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227972B2

Reaction notes

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