Trifluoroacetic acid → HCID 57748288, compound

HRID 906195Notes

Reaction equation

HRID 906195 reaction equation
[NH2:1][C:2]1[C:3](I)=[CH:4][C:5]([C:12]([F:15])([F:14])[F:13])=[C:6]([CH:11]=1)[C:7]([O:9]C)=[O:8].[NH2:17]C1C(C(F)(F)F)=C(C=CC=1I)C(OC)=O.FC(F)(F)[C:35]([OH:37])=O.[CH3:40][CH2:41][C:42](=O)[CH2:43][CH3:44].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[NH2:17][C:35]([C:3]1[C:2]([NH:1][CH:42]([CH2:43][CH3:44])[CH2:41][CH3:40])=[CH:11][C:6]([C:7]([OH:9])=[O:8])=[C:5]([C:12]([F:15])([F:14])[F:13])[CH:4]=1)=[O:37]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7288Ethyl ketoneHCID 5049666Sodium triacetoxyborohydrideHCID 67402411HCID 67402411, compoundHCID 67403170HCID 67403170, compound

Product 1

HCID 57748288HCID 57748288, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of methyl 5-amino-4-iodo-2-(trifluoromethyl)benzoate (desired) and methyl 3-amino-4-iodo-2-(trifluoromethyl)benzoate as obtained in step 4 (392 mg, 1.14 mmol) was dissolved in 1,2-dichloroethane (12 mL) and was treated with trifluoroacetic acid (0.5 mL, 6.73 mmol), 3-pentanone (0.36 mL, 3.40 mmol) and sodium triacetoxyborohydride (724 mg, 3.42 mmol) at 45° C. for 0.5 h. GCMS indicated complete conversion of desired isomer to required product. After a further 0.5 h at 45° C., the reaction mixture was cooled to ambient temperature and was quenched with 1N sodium hydroxide (5 mL) and saturated sodium bicarbonate and was partitioned with dichloromethane. The aqueous portion was extracted with dichloromethane. The combined organic portion was washed with brine, dried over magnesium sulfate, then filtered and concentrated to afford a yellow oil which was purified by column chromatography (silica gel, 10-40% dichloromethane in hexanes) to afford pure methyl 4-iodo-5-(pentan-3-ylamino)-2-(trifluoromethyl)benzoate (330 mg, 0.795 mmol, 70% yield) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 6.79 (s, 1H), 4.44 (d, 1H), 3.92 (s, 3H), 3.44-3.34 (m, 1H), 1.73-1.48 (m, 4H), 0.95 (t, 6H); GCMS for C14H17F31NO2: 415 (M+).

Workup

  1. customas obtained in step 4 (392 mg, 1.14 mmol)

Sources & evidence

ORD record
ord-4f11eafd1d1d488aa95517a0219b16a8
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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