Methanol → HCID 68915996, compound

HRID 1435775Notes

Reaction equation

HRID 1435775 reaction equation
CP(C)C.C1(OP([N:21]2[C:29]3[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=3)[C:23]([C@H:31]3[C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[C@H:33]([N:40]=[N+]=[N-])[CH2:32]3)=[CH:22]2)(=O)OC2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)C.CO>N1C=CC=CC=1.[OH-].[NH4+].C(N(CC)CC)C>[Cl:30][C:26]1[CH:25]=[C:24]2[C:29](=[CH:28][CH:27]=1)[NH:21][CH:22]=[C:23]2[C@H:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C@H:33]([NH2:40])[CH2:32]1

Participants

8

Reactant 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 68983TrimethylphosphineHCID 86618894HCID 86618894, compound

Product 1

HCID 68915996HCID 68915996, compound

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8471TriethylamineSolventHCID 14923Ammonium HydroxideSolvent

Procedure

32 g Trimethyl phosphine was added over 2 hours to 19 g [3-((1R,3R)-3-azido-indan-1-yl)-5-chloro-indol-1-yl]-phosphonic acid diphenyl ester in 100 mL pyridine and 36 mL 9N ammonium hydroxide at room temperature. The reaction mixture was stirred over night at room temperature and concentrated in vacuo. Ethyl acetate and water were added. The mixture was made basic with aqueous NaOH and filtered. The organic phase was concentrated in vacuo and was dissolved in ethyl acetate again. The ethyl acetate solution was extracted with 2×250 mL 2N methanesulfonic acid. The aqueous phase was made basic with 9N NaOH to form a precipitate, which was subjected to flash chromatography (ethyl acetate, methanol, triethylamine, silica gel) to give 0.6 g (1R,3R)-3-(5-chloro-1H-indol-3-yl)-indan-1-ylamine. The ethyl acetate phase from above was concentrated in vacuo and was dissolved in 100 mL methanol and 10 mL 30% NaOMe in methanol was added. The reaction mixture was stirred 2 hours at room temperature, concentrated in vacuo and purified by flash chromatography (ethyl acetate, methanol, triethylamine, silica gel) to give further 0.45 g (1R,3R)-3-(5-chloro-1H-indol-3-yl)-indan-1-ylamine.

Workup

  1. concentrationconcentrated in vacuo
  2. additionEthyl acetate and water were added
  3. filtrationfiltered
  4. concentrationThe organic phase was concentrated in vacuo
  5. dissolutionwas dissolved in ethyl acetate again
  6. extractionThe ethyl acetate solution was extracted with 2×250 mL 2N methanesulfonic acid
  7. customto form a precipitate, which

Sources & evidence

ORD record
ord-c9c493e5a06e4e65a133d7a7f2f76662
Source dataset
uspto-grants-2009_11
Patent number
US07618967B2

Reaction notes

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