3-Mercaptopropionic Acid → 3-(((2,2-Difluorocyclopropyl)methyl)thio)propanoic acid

HRID 512761Notes

Reaction equation

[OH-].[K+].Br[CH2:4][CH:5]1[CH2:7][C:6]1([F:9])[F:8].[SH:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14]>CO>[F:8][C:6]1([F:9])[CH2:7][CH:5]1[CH2:4][S:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14]

Participants

Conditions

Temperature: 65 °C

Procedure

Powdered potassium hydroxide (423 mg, 7.54 mmol) and 2-(bromomethyl)-1,1-difluorocyclopropane (657 mg, 3.84 mmol) were sequentially added to a stirred solution of 3-mercaptopropanoic acid (400 mg, 3.77 mmol) in methanol (2 mL) at room temperature. The resulting white suspension was stirred at 65° C. for 3 hours and quenched with aqueous hydrochloric acid (1 N) and diluted with ethyl acetate. The organic phase was separated and the aqueous phase extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo to give the title molecule as a colorless oil (652 mg, 84%): IR (thin film) 3025, 2927, 2665, 2569, 1696 cm−1; 1H NMR (400 MHz, CDCl3) δ 2.85 (t, J=7.0 Hz, 2H), 2.82-2.56 (m, 4H), 1.88-1.72 (m, 1H), 1.53 (dddd, J=12.3, 11.2, 7.8, 4.5 Hz, 1H), 1.09 (dtd, J=13.1, 7.6, 3.7 Hz, 1H); ESIMS m/z 195 ([M−H]−).

Workup

customquenched with aqueous hydrochloric acid (1 N)
additiondiluted with ethyl acetate
customThe organic phase was separated
extractionthe aqueous phase extracted with ethyl acetate (2×50 mL)
dry with materialThe combined organic extracts were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-8451ac08cb3a4e578f5c347690a1b4de
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102655B2

Reaction notes

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