Acetic Acid → HCID 69337519, compound

HRID 1179081Notes

Reaction equation

HRID 1179081 reaction equation
[CH3:1][N:2]([CH3:16])[C:3]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][CH2:7][C:6](=O)[CH2:5][CH2:4]1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O)(=O)C.[CH3:28][O:29][C:30](=[O:44])[C@H:31]([CH2:33][C:34]1[C:42]2[C:37](=[CH:38][CH:39]=[C:40]([F:43])[CH:41]=2)[NH:36][CH:35]=1)[NH2:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:59][Si](C)(C)C.C1(N)C(F)=C(F)C(F)=C(N)C=1F.[ClH:76].Cl>ClCCCl.CC(=O)CC.CC(C)=O>[ClH:59].[ClH:76].[CH3:28][O:29][C:30](=[O:44])[CH:31]([NH:32][CH:6]1[CH2:7][CH2:8][C:3]([N:2]([CH3:16])[CH3:1])([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:4][CH2:5]1)[CH2:33][C:34]1[C:42]2[C:37](=[CH:38][CH:39]=[C:40]([F:43])[CH:41]=2)[NH:36][CH:35]=1

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 6397ChlorotrimethylsilaneHCID 24436Sodium SulfateHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 114244924-(Dimethylamino)-4-phenylcyclohexan-1-oneHCID 13653067HCID 13653067, compound

Product 1

HCID 69337519HCID 69337519, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 22381885HCID 22381885, compoundSolvent

Procedure

4-Dimethylamino-4-phenylcyclohexanone (935 mg), sodium sulfate (4 g) and glacial acetic acid (245 μl, 4.4 mmol.) were added under argon to rac-5-fluorotryptophan methyl ester (1,030 mg) in 1,2-dichloroethane (approx. 40 ml). After one hour's stirring at RT, sodium triacetoxyborohydride (1.4 g, 6.5 mmol.) was added. The mixture was stirred for three days at RT. For working up, the mixture was concentrated, the residue was taken up in ethyl acetate (40 ml) and 1N NaOH (35 ml), the phases were separated and the aqueous phase was extracted three times with ethyl acetate (10 ml each time). The combined extracts were dried and concentrated and the residue obtained (1.73 g) purified by flash chromatography (eluant: MeOH/EtOAc 1:3). The nonpolar diastereomer obtained (911 mg, m.p. 55-62° C.) was dissolved in 2-butanone/acetone (7 ml/1 ml) and converted with chlorotrimethylsilane (174 μl) into the corresponding dihydrochloride (beige solid; 135 mg; m.p. 172-182° C.).

Workup

  1. stirringThe mixture was stirred for three days at RT
  2. concentrationthe mixture was concentrated
  3. custom1N NaOH (35 ml), the phases were separated
  4. extractionthe aqueous phase was extracted three times with ethyl acetate (10 ml each time)
  5. customThe combined extracts were dried
  6. concentrationconcentrated
  7. customthe residue obtained (1.73 g)
  8. custompurified by flash chromatography (eluant: MeOH/EtOAc 1:3)
  9. customThe nonpolar diastereomer obtained (911 mg, m.p. 55-62° C.)

Sources & evidence

ORD record
ord-2b14259afcc049d68308209818c22a81
Source dataset
uspto-grants-2007_10
Patent number
US07276518B2

Reaction notes

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