Oxygen → HCID 86639767, compound

HRID 659896Notes

Reaction equation

[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].O=O.Br[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH:10]=1.CON(C)[C:28](=[O:80])[C@H:29]([O:72]CC1C=CC=CC=1)[C@@H:30]([O:64][CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)[C@H:31]([O:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[C:32]([OH:55])([CH2:44][O:45][CH2:46][C:47]1[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=1)[CH2:33][O:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1.[Al].O1C[CH2:86][CH2:85][CH2:84]1>C(OCC)C>[CH2:1]([O:72][CH:29]1[C@@H:30]([O:64][CH2:65][C:66]2[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=2)[C@H:31]([O:56][CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[C:32]([CH2:44][O:45][CH2:46][C:47]2[CH:48]=[CH:49][C:50]([O:53][CH3:54])=[CH:51][CH:52]=2)([CH2:33][O:34][CH2:35][C:36]2[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)[O:55][C:28]1([C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH:10]=1)[OH:80])[C:2]1[CH:86]=[CH:85][CH:84]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 10 °C

Procedure

n-Butyl lithium (462 microL, 2.5 M/hexanes, 3.0 equivalents) was added dropwise (1 drop every 5 seconds) to an oxygen degassed solution (placed in a pre dried Biotage™ microwave vial 10-20 mL sealed with its cap and placed under a positive stream of nitrogen gas) of 4-Bromo-1-fluoro-2-(4-methoxy-benzyl)-benzene (341 mg, 3 equivalents) in anhydrous tetrahydrofuran (1.4 mL) at −78° C. under nitrogen. The resulting solution was stirred at this temperature for 1 hour. Then a solution of (2R,3S,4S)-2,3,4-tris-benzyloxy-5-hydroxy-6-(4-methoxy-benzyloxy)-5-(4-methoxy-benzyloxymethyl)-hexanoic acid methoxy-methyl-amide (I-1g) (300 mg, 0.385 mmol) in anhydrous tetrahydrofuran (0.70 mL) was added dropwise very slowly (1 drop every 5 seconds) and the resulting mixture was stirred at −78° C. for an additional hour before warming to 10° C. over 12 hours (put in a deep Dewar covered with aluminum foil to maintain cold temperature; size of Dewar: external diameter 10 cm, internal diameter 8 cm, height 9 cm). The reaction was diluted with diethyl ether and quenched by the dropwise addition of aqueous 1N hydrochloric acid solution. The resulting biphasic mixture was stirred at room temperature for 15 minutes. The organic phase was separated, washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (eluting with a gradient of 10 to 40% ethyl acetate in heptane) to afford the product as a mixture of isomers (199 mg, 55% yield).

Workup

customdried Biotage™ microwave vial 10-20 mL
customsealed with its
customcap
customat −78° C.
stirringthe resulting mixture was stirred at −78° C. for an additional hour
temperatureto maintain cold temperature
customquenched by the dropwise addition of aqueous 1N hydrochloric acid solution
stirringThe resulting biphasic mixture was stirred at room temperature for 15 minutes
customThe organic phase was separated
washwashed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude residue was purified by flash chromatography over silica gel (
washeluting with a gradient of 10 to 40% ethyl acetate in heptane)
customto afford the product
additionas a mixture of isomers (199 mg, 55% yield)

Sources & evidence

ORD record: ord-6ad9e7a35b864ae994a92cc60b1e9548
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08080580B2

Reaction notes

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