Sulfuric Acid → (2R)-2-bromo-3-cyclohexylpropanoic acid

HRID 31085Notes

Reaction equation

N([O-])=O.[Na+].N[C@H:6]([CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[C:7]([OH:9])=[O:8].[Br-:17].[K+].S(=O)(=O)(O)O>O>[Br:17][C@H:6]([CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[C:7]([OH:9])=[O:8]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of sodium nitrite (0.45 g, 6.5 mmol) in water (1.2 ml) was added dropwise at 0° C. over 4 hours to a stirred mixture of (R)-α-aminocyclohexanepropionic acid (1 g, 5.8 mmol), potassium bromide (2.3 g, 19.2 mmol) and concentrated sulphuric acid (0.66 ml) in water (7 ml). The mixture was stirred for 5 hours at 0° C. then at ambient temperature for 16 hours. The product was extracted into diethyl ether (4×20 ml) then the combined ethereal layers were washed with saturated aqueous sodium chloride solution (2×50 ml), dried (MgSO4) and the solvent removed in vacuo. The residue was purified by chromatography over silica gel eluting with a gradient of methanol: dichloromethane 1:50→1:20. Appropriate fractions were combined and the solvents removed in vacuo to give (R)-α-bromocyclohexanepropionic acid as a pale yellow oil 0.374 g, (27%). TLC (single spot, Rf=0.45, 10% methanol in dichloromethane), HPLC-MS (single main peak with Rt=8.88 mins, 234.1/236.1 [M+H]+, 257.2/259.2 [M+Na]+).

Workup

waitat ambient temperature for 16 hours
extractionThe product was extracted into diethyl ether (4×20 ml)
washthe combined ethereal layers were washed with saturated aqueous sodium chloride solution (2×50 ml)
dry with materialdried (MgSO4)
customthe solvent removed in vacuo
customThe residue was purified by chromatography over silica gel eluting with a gradient of methanol: dichloromethane 1:50→1:20
customthe solvents removed in vacuo

Sources & evidence

ORD record: ord-0a6e49cd2cd047c39f380c8c344d1c42
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07425562B2

Reaction notes

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