Sulfuric Acid → HCID 70209846, compound

HRID 987333Notes

Reaction equation

HRID 987333 reaction equation
[F:1][C:2]([F:8])([F:7])[CH:3]([CH3:6])[CH:4]=O.S(=O)(=O)(O)O.Cl.[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28]([CH2:31][C@H:32]([O:36][CH2:37][CH3:38])[C:33]([OH:35])=[O:34])=[CH:27][CH:26]=2)=[CH:18][CH:17]=1.[BH4-].[Na+]>O1CCCC1.ClCCl.CO>[CH2:37]([O:36][C@@H:32]([CH2:31][C:28]1[CH:29]=[CH:30][C:25]([O:24][CH2:23][CH2:22][C:19]2[CH:20]=[CH:21][C:16]([NH:15][CH2:4][CH:3]([CH3:6])[C:2]([F:8])([F:7])[F:1])=[CH:17][CH:18]=2)=[CH:26][CH:27]=1)[C:33]([OH:35])=[O:34])[CH3:38]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 27821883,3,3-trifluoro-2-methylpropanalHCID 4311764Sodium borohydrideHCID 86595065HCID 86595065, compound

Product 1

HCID 70209846HCID 70209846, compoundYield 54.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2-(Trifluoromethyl)propionaldehyde (0.0724 g; 0.574 mmole) was dissolved in tetrahydrofurane (3 ml) and sulfuric acid (4 M; 0.041 ml; 0.164 mmole) was added under stirring, followed by addition of 3-{4-[2-(4-aminophenyl)ethoxy]phenyl}-(S)-2-ethoxypropanoic acid hydro chloride (described in Example 56a) (0.2 g; 0.547 mmole) dissolved in tetrahydrofurane (2 ml). The reaction mixture was stirred for 10 minutes, then cooled to 0° C in an ice-bath and sodium borohydride (0.042 g; 1.10 mmole) was added. After addition, the cooling bath was removed. The mixture was stirred overnight and then evaporated to remove tetrahydrofurane. Ethyl acetate and water were added into the residue and the organic phase was separated, washed with brine, dried with magnesium sulfate. The solvent was then evaporated. Chromatography on silica gel(Isolute, SI ) using dichloromethane and then 1% methanol in dichloromethane as eluant gave 0.13 g (40% yield) of (S)-2-ethoxy-3-(4-{2-[4-(3,3,3-trifluoro-2-methyl-(R/S)-propylamino)phenyl]ethoxy}phenyl)propanoic acid.

Workup

  1. stirringThe reaction mixture was stirred for 10 minutes
  2. additionAfter addition
  3. customthe cooling bath was removed
  4. stirringThe mixture was stirred overnight
  5. customevaporated
  6. customto remove tetrahydrofurane
  7. additionEthyl acetate and water were added into the residue
  8. customthe organic phase was separated
  9. washwashed with brine
  10. dry with materialdried with magnesium sulfate
  11. customThe solvent was then evaporated

Sources & evidence

ORD record
ord-41bdc8b91dfc4e8eb0437f61bfc6f5ce
Source dataset
uspto-grants-2003_10
Patent number
US06630600B1

Reaction notes

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