Methanol → HCID 59822021, compound

HRID 1665835Notes

Reaction equation

HRID 1665835 reaction equation
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[CH:12]1([C:17]2[C:26]3[C:25](=[O:27])[CH2:24][C:23]([CH3:29])([CH3:28])[CH2:22][C:21]=3[N:20]=[C:19]([CH:30]([CH3:32])[CH3:31])[C:18]=2[C:33](=[O:44])[C:34]2[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1.CO>C1COCC1>[CH:12]1([C:17]2[C:26]3[C@@H:25]([OH:27])[CH2:24][C:23]([CH3:28])([CH3:29])[CH2:22][C:21]=3[N:20]=[C:19]([CH:30]([CH3:32])[CH3:31])[C:18]=2[C:33]([C:34]2[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:41])[F:42])=[CH:36][CH:35]=2)=[O:44])[CH2:13][CH2:14][CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 887MethanolHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 59822026HCID 59822026, compound

Product 1

HCID 59822021HCID 59822021, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

140 mg (0.96 mmol, 0.08 eq.) of (1R,2S)-1-aminoindan-2-ol are initially charged in 440 ml of THF, and 7.80 g (47.8 mmol, 4.0 eq.) of borane N,N-diethylaniline complex are added at room temperature. After the evolution of gas has ceased, the mixture is cooled to 0° C. and 5.47 g (12 mmol, 1 eq.) of the compound from Example 2A, dissolved in 40 ml of THF, are added. With stirring, the mixture is allowed to warm to room temperature over a period of 28 h. After the reaction has ended, 20 ml of methanol are added to the reaction mixture and the mixture is concentrated. The residue is partitioned between 150 ml of water and 150 ml of ethyl acetate. The aqueous phase is extracted twice with in each case 100 ml of ethyl acetate. The combined organic phases are washed with 50 ml of saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product is then purified by chromatography (silica gel, mobile phase: isohexane/ethyl acetate 4:1).

Workup

  1. addition7.80 g (47.8 mmol, 4.0 eq.) of borane N,N-diethylaniline complex are added at room temperature
  2. additionare added
  3. temperatureto warm to room temperature over a period of 28 h
  4. concentrationthe mixture is concentrated
  5. customThe residue is partitioned between 150 ml of water and 150 ml of ethyl acetate
  6. extractionThe aqueous phase is extracted twice with in each case 100 ml of ethyl acetate
  7. washThe combined organic phases are washed with 50 ml of saturated sodium chloride solution
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product is then purified by chromatography (silica gel, mobile phase: isohexane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-dbc4da9abb794cd3bd034858ad56f971
Source dataset
uspto-grants-2011_10
Patent number
US08039629B2

Reaction notes

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