[(Benzyloxy)methyl]tributylstannane → 2-Benzyloxy-1-[6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazol-5-yl]-ethanol

HRID 1010043Notes

Reaction equation

[CH2:1]([O:8][CH2:9][Li])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Sn](COCC1C=CC=CC=1)(CCCC)(CCCC)CCCC.[Li]CCCC.[Br:38][C:39]1[CH:44]=[CH:43][C:42]([NH:45][C:46]2[C:47]([CH:56]=[O:57])=[CH:48][C:49]3[NH:53][CH:52]=[N:51][C:50]=3[C:54]=2[F:55])=[C:41]([Cl:58])[CH:40]=1>C1COCC1>[CH2:1]([O:8][CH2:9][CH:56]([C:47]1[C:46]([NH:45][C:42]2[CH:43]=[CH:44][C:39]([Br:38])=[CH:40][C:41]=2[Cl:58])=[C:54]([F:55])[C:50]2[N:51]=[CH:52][NH:53][C:49]=2[CH:48]=1)[OH:57])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of benzyloxymethyllithium in THF (2 mL, prepared from n-Bu3SnCH2OBn (505 mg, 1.23 mmol) and n-BuLi (0.49 mL, 1.22 mmol, 2.5 M solution in hexane) by the procedure reported in J. Am. Chem. Soc. 1978, 100, 1481) is added a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f (51 mg, 0.14 mmol) in THF (3 mL) at −78° C. The resulting solution is stirred for 1 hour at −78° C. The reaction is quenched with saturated aqueous NH4Cl, and extracted with EtOAc. The organic layer is dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (100% CH2Cl2 to 3% MeOH in CH2Cl2) to afford the desired product (46 mg, 68%): MS APCI (+) m/z 490, 492 (M+, Br pattern) detected.

Workup

customThe reaction is quenched with saturated aqueous NH4Cl
extractionextracted with EtOAc
dry with materialThe organic layer is dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by flash chromatography (100% CH2Cl2 to 3% MeOH in CH2Cl2)

Sources & evidence

ORD record: ord-e72f2624f9a44debb14d4c016b1aeb4f
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07973170B2

Reaction notes

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