Formic Acid → HCID 86701124, compound

HRID 1396293Notes

Reaction equation

HRID 1396293 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@H:17]([CH:18]([OH:23])[C:19]([F:22])([F:21])[F:20])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:24](CC=C)[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[S:14]2)[C@H:10]1[O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(O)=O.C([O-])(O)=O.[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.ClCCl>[CH2:1]([O:8][C@@H:9]1[C@@H:17]([CH:18]([OH:23])[C:19]([F:20])([F:22])[F:21])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[S:14]2)[C@H:10]1[O:35][CH2:36][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 284Formic Acid2×HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 69093784HCID 69093784, compound

Product 1

HCID 86701124HCID 86701124, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 141 (1.6 g, 2.6 mmol) in 1,4-dioxane (20 mL) was added Pd(PPh3)4 (760 mg, 0.6 mmol), triethylamine (664 mg, 6.5 mmol) and formic acid (242 mg, 5.2 mmol) at room temperature under nitrogen atmosphere. The resulting mixture was heated to 60° C. for 20 minutes, and followed by addition of additional formic acid (605 mg, 26 mmol). After stirred overnight at 60° C., removal of volatiles gave a residue, which was dissolved into dichloromethane (50 mL) and neutralized with saturated aqueous NaHCO3 solution (30 mL). The aqueous layer was extracted with dichloromethane (3×30 mL). The combined organic layer was dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography with 20%-30% ethyl acetate in petroleum ether to afford 142 as colorless oil (1.1 g, 77%). (ES, m/z): [M+H]+ 569.0; 1H NMR (300 MHz, CDCl3) δ 7.34-7.23 (m, 10H), 6.17-6.13 (m, 1H), 4.62-4.46 (m, 2H), 4.43-4.00 (m, 4H), 3.91-3.73 (m, 3H), 1.52 (s, 9H).

Workup

  1. customremoval of volatiles
  2. customgave a residue, which
  3. extractionThe aqueous layer was extracted with dichloromethane (3×30 mL)
  4. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography with 20%-30% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-0cec8106a5df4fc5b62801e43b6a25ef
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

Loading…