Trifluoroacetic acid → HCID 42610584, compound

HRID 1632106Notes

Reaction equation

HRID 1632106 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=3)[C:8]=2[OH:24])=[CH:4][CH:3]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=[O:35]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:7]2[C:8]([OH:24])=[C:9]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=3)[C:10]([O:13][CH3:14])=[CH:11][CH:12]=2)=[O:35])=[CH:25][CH:26]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 12052Triethylsilane2×HCID 58020205HCID 58020205, compound

Product 1

HCID 42610584HCID 42610584, compound

Procedure

Synthesis of 3-(4-Fluoro-benzyl)-6-methoxy-3′-nitro-biphenyl-2-ol (P-099) In an 8 mL vial equipped with a stir bar was placed I-246 (60 mg, 0.163 mmol) and triethylsilane (350 μL). The mixture was cooled in an ice-water bath and then TFA (350 μL) was added. The reaction mixture was warmed to room temperature and reacted for 17 hours. After this time period, additional triethylsilane (1.1 mL) and TFA (1.1 mL) was introduced and the reaction mixture was heated to 60° C. in an oil bath for 24 hours. The reaction mixture was concentrated by a stream of N2, quenched with water (20 mL) and extracted with dichloromethane (2×30 mL). The organic portions were combined, washed with brine (30 mL), dried (MgSO4) and concentrated. The residue was purified by SiO2 column chromatography utilizing 15% EtOAc/hexanes as the eluent to produce 18.9 mg of P-099 as a viscous, tan oil in 33% yield. 1H NMR (400 MHz, CDCl3) δ 3.72 (s, 3H), 3.94 (s, 2H), 4.73 (s, 1H), 6.55 (d, J=8 Hz, 1H), 6.96-7.00 (m, 2H), 7.01 (d, J=8 Hz, 1H), 7.19-7.22 (m, 2H), 7.63 (t, J=7 Hz, 1H), 7.69 (dt, J=8, 2 Hz, 1H), 8.22-8.26 (m, 2H) ppm. MS (APCI−): 352.1 (M−1); LC-MS: 98%.

Workup

  1. customvial equipped with a stir bar
  2. temperatureThe mixture was cooled in an ice-water bath
  3. customreacted for 17 hours
  4. temperaturethe reaction mixture was heated to 60° C. in an oil bath for 24 hours
  5. concentrationThe reaction mixture was concentrated by a stream of N2
  6. customquenched with water (20 mL)
  7. extractionextracted with dichloromethane (2×30 mL)
  8. washwashed with brine (30 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customThe residue was purified by SiO2 column chromatography
  12. customto produce 18.9 mg of P-099 as a viscous, tan oil in 33% yield

Sources & evidence

ORD record
ord-6cf55a51ec2d4d6d9e224549115640fb
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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