Bromomethylcyclopropane → HCID 178527322, compound

HRID 853131Notes

Reaction equation

[F:1][C:2]([F:33])([F:32])[C:3]([C@H:16]1[CH2:21][CH2:20][C@H:19]([NH:22][S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH2:18][CH2:17]1)([O:8][Si](CC)(CC)CC)[C:4]([F:7])([F:6])[F:5].[Li][CH2:35][CH2:36][CH2:37][CH3:38].BrCC1CC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCCCCC>[CH:37]1([CH2:38][N:22]([C@H:19]2[CH2:20][CH2:21][C@H:16]([C:3]([OH:8])([C:2]([F:33])([F:1])[F:32])[C:4]([F:7])([F:6])[F:5])[CH2:17][CH2:18]2)[S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:24])=[O:25])[CH2:35][CH2:36]1

Participants

Conditions

Temperature: -40 °C

Procedure

A solution of 500 mg (0.89 mmol) of trans N-[4-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-cyclohexyl]-benzenesulfonamide (example 1.3) in 10 mL of THF was cooled to −78° C. and treated dropwise with 0.72 mL of a 1.6 M BuLi solution in hexane. The solution was warmed to −40° C. within 30 min, treated with 0.43 mL (4.45 mmol) of bromomethylcyclopropane, allowed to reach RT and then refluxed overnight. An excess of TBAF was added and the mixture was stirred for an additional hour. Distribution of the crude mixture between a saturated aqueous solution of NH4Cl and Et2O, drying of the combined organic phases over Na2SO4, evaporation and chromatography on silica gel with CH2Cl2 gave 200 mg (49%) of trans N-cyclopropylmethyl-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-cyclohexyl]-benzenesulfonamide, as a colorless viscous oil, MS: 460 (M+H)+.

Workup

customto reach RT
temperaturerefluxed overnight
dry with materialDistribution of the crude mixture between a saturated aqueous solution of NH4Cl and Et2O, drying of the combined organic phases over Na2SO4, evaporation and chromatography on silica gel with CH2Cl2

Sources & evidence

ORD record: ord-d66b50c193ac4f9fbbca91cb20f6ac6d
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07253282B2

Reaction notes

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