Trifluoroacetic acid → Ethyl acetate methanol ammonia

HRID 1467865Notes

Reaction equation

C(O)(=O)/C=[CH:3]/[C:4]([OH:6])=[O:5].[CH:9]1(C[N:13](C2CCN([C:33](=[O:41])C(NC)CC(C)C)CC2)S(C2C=CC=C(C(F)(F)F)C=2)(=O)=O)C[CH2:10]1.C(OC(=O)N(C)C(C(N1CCC(NS(C2C=CC=C(C(F)(F)F)C=2)(=O)=O)CC1)=O)CC(C)C)(C)(C)C.C1(CBr)CC1.FC(F)(F)C(O)=O>>[C:4]([O:6][CH2:9][CH3:10])(=[O:5])[CH3:3].[CH3:33][OH:41].[NH3:13]

Participants

Reactant 4

HCID 6422Trifluoroacetic acid

HCID 81503Bromomethylcyclopropane

HCID 68985444HCID 68985444, compound

HCID 86629769HCID 86629769, compound

Product 1

HCID 21873639Ethyl acetate methanol ammonia

Procedure

(2S) N-Cyclopropylmethyl-N-[1-(4-methyl-2-methylamino-pentanoyl)piperidin-4-yl]-3-trifluoromethylbenzenesulfonamide fumarate (7): Methyl-{3-methyl-1-[4-(3-trifluoromethylbenzenesulfonylamino)piperidine-1-carbonyl]butyl}-carbamic acid tert-butyl ester (3) (0.5 g, 0.93 mmol) was alkylated with cyclopropylmethyl bromide using method B. The product was treated with trifluoroacetic acid and worked up according to method B. Flash chromatography (SiO2, ethyl acetate:methanol:ammonia 250:20:2) gave the free base as a colourless gum (88 mg). This gum was converted to the fumarate salt to give the title compound (7) (80 mg, 14%) as a white solid. TLC (SiO2, ethyl acetate: methanol: ammonia, 250:40:4): Rf=0.31 (detection UV and potassium iodoplatinate). LC: 100%. MS (m/z): 490.2, 491.2 (M+H). 1H NMR (400 MHz, DMSO-d6): δ 8.20 (1H, d, J=7 Hz), 8.12 (1H, s), 8.07 (1H, d, J=7 Hz), 7.85 (1H, t, J=7 Hz), 6.56 (2H, s), 4.45 (1H, m), 4.00-3.05 (5H, m), 2.65 (2H, m), 2.30 and 2.22 (3H, 2s), 1.73-1.48 (5H, m), 1.35 (2H, m), 0.95 (1H, m), 0.85 (6H, m), 0.45 (2H, m), 0.25 (2H, m).

Sources & evidence

ORD record: ord-2f610f63b72741cdb1af2cda9852c025
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09000174B2

Reaction notes

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