Formic Acid → HCID 11281200, compound

HRID 1437515Notes

Reaction equation

HRID 1437515 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[C:9](=O)[CH2:8][CH2:7][CH2:6][C:5]2=1.[CH3:16][C@@H:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)=O.C(N(CC)CC)C>C1(C)C=CC=CC=1.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[C@H:9]([NH:24][C@@H:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH3:16])[CH2:8][CH2:7][CH2:6][C:5]2=1

Participants

8

Reactant 5

HCID 284Formic AcidHCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 6431891-Phenethylamine, (+)-HCID 7085296-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one

Product 1

HCID 11281200HCID 11281200, compoundYield 68.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one (50 mg, 0.19 mmol), (R)-α-methylbenzylamine (23 mg, 0.19 mmol), and p-toluenesulfonic acid (5 mg) in toluene (15 mL) were refluxed with a Dean-Stark trap for 16 hours. The mixture was concentrated and the residue dried under high vacuum. The residue was dissolved in dichloromethane (3 mL) before formic acid (0.036 mL, 0.95 mmol), triethylamine (0.052 mL, 0.38 mmol), and (S)-RuCl[(1R,2R)-p-TsNCH(C6He)CH(C6H6)NH2](η-benzene) (16 mg, 0.038 mmol) were added and stirred for one hour at room temperature. (S)-RuCl[(1R,2R)-p-TsNCH(C6H6)CH(C6H6)NH2](η-benzene) was prepared as described in Journal of American Chemical Society 1996, 118, 2521-2522, and references therein, incorporated herein by reference with regard to such synthesis. The mixture was diluted with dichloromethane (10 mL) and washed with saturated sodium bicarbonate (10 mL). The organic phase was applied directly to a silica gel chromatography column and was eluted with 5% ethyl acetate in dichloromethane. Appropriate fractions were concentrated to yield 48 mg (68%, 90% de) of (1R)-6-bromo-N-[(1R)-1-phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-1-amine. 1H NMR (DMSO-d6): δ 10.84 (s, 1H), 7.47 (m, 3H), 7.32 (m, 3H), 7.22 (t, 1H), 7.12 (d, 1H), 4.10 (m, 1H), 3.78 (m, 1H), 2.50 (m under DMSO, 2H), 2.16 (bs, 1H), 1.87 (m, 1H), 1.76 (m, 1H), 1.59 (m, 1H), 1.49 (m, 1H), 1.31 (d, 3H); MS m/z 368 (M−1). (1R)-6-bromo-N-[(1R)-1-phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-1-amine (48 mg, 90% de) was dissolved in ethyl ether (2 mL) before 1 M HCl in ether (2 mL) was added dropwise. The resulting precipitate was collected by filtration to yield 36 mg of a yellow solid. The solid was dissolved in hot methanol (2 mL). The solution was allowed to cool and ethyl ether added dropwise until the solution became cloudy. Crystals precipitated and were collected by filtration to yield 16 mg (30%, 100% de) of (1R)-6-bromo-N-[(1R)-1-phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-1-amine hydrochloride. 1H NMR (DMSO-d6): δ 11.66 (s, 1H), 9.86 (bs, 1H), 9.29 (m, 1H), 7.76 (d, 2H), 7.66 (s, 1H), 7.36-7.48 (m, 4H), 7.24 (d, 1H), 4.73 (m, 1H), 4.55 (m, 1H), 2.63 (m, 2H), 2.09 (m, 1H), 1.96 (m, 2H), 1.79 (m, 1H), 1.67 (d, 3H). MS m/z 367, 369 (M−1).

Workup

  1. temperaturewere refluxed with a Dean-Stark trap for 16 hours
  2. concentrationThe mixture was concentrated
  3. customthe residue dried under high vacuum
  4. additionwere added
  5. customincorporated herein by reference with regard to such synthesis
  6. washwashed with saturated sodium bicarbonate (10 mL)
  7. washwas eluted with 5% ethyl acetate in dichloromethane
  8. concentrationAppropriate fractions were concentrated

Sources & evidence

ORD record
ord-4841742d183a4c10a64b26fc4ba998cb
Source dataset
uspto-grants-2009_11
Patent number
US07622494B2

Reaction notes

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