Formic Acid → HCID 59846451, compound

HRID 1363233Notes

Reaction equation

HRID 1363233 reaction equation
C(N(CC)CC)C.C(O)=O.[F:11][C:12]([F:29])([F:28])[C:13]([NH:15][C@H:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:26])[CH:24]=2)[C:19](=[O:27])[CH2:18][CH2:17]1)=[O:14]>CN(C=O)C>[F:29][C:12]([F:11])([F:28])[C:13]([NH:15][C@H:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:26])[CH:24]=2)[C@H:19]([OH:27])[CH2:18][CH2:17]1)=[O:14]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 59846309HCID 59846309, compound

Product 1

HCID 59846451HCID 59846451, compoundYield 16.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To ice bath-cooled triethylamine (13.3 mL, 95.2 mmol, 7.4 equiv.) was added dropwise formic acid (3.65 mL, 95.2 mmol, 7.4 equiv.). The reaction solution was stirred at RT for 20 min. A solution of (R)-2,2,2-trifluoro-N-(7-fluoro-4-oxo-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide (3.54 g, 12.9 mmol, 1 equiv) in DMF (10 ml) and Noyori catalyst (R,R form) (204.3 mg, 2.5 mol %) were added and stirred at RT overnight. TLC was checked and found only small amount of product formed. The reaction solution was stirred at 40° C. for 16 h. TLC showed reaction completed. The solvents were evaporated off The residue was treated with CH2Cl2 to result a white solid precipitate, which was collected on funnel and washed with small amount of CH2Cl2 (2.15 g). The filtrate gave additional 0.58 g of product after chromatography (ISCO, 30-40% EtOAc-hexane). Total: 2.73 g (77%). 1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 7.52 (q, 1H), 7.13 (m, 1H), 6.85 (dd, 1H), 5.36 (d, 1H), 5.05 (m, 1H), 4.55-4.62 (m, 1H), 2.06-2.14 (m, 2H), 1.64-1.80 (m, 2H).

Workup

  1. stirringstirred at RT overnight
  2. customformed
  3. stirringThe reaction solution was stirred at 40° C. for 16 h
  4. customreaction
  5. customThe solvents were evaporated off The residue
  6. additionwas treated with CH2Cl2
  7. customto result a white solid precipitate, which
  8. customwas collected on funnel
  9. washwashed with small amount of CH2Cl2 (2.15 g)

Sources & evidence

ORD record
ord-a89e83ed1c464f01b9fc17fb4c27c077
Source dataset
uspto-grants-2011_02
Patent number
US07884109B2

Reaction notes

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