Tetrahydrofuran → HCID 58003035, compound

HRID 1516742Notes

Reaction equation

HRID 1516742 reaction equation
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.O1CCCC1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:36]([CH:37]([OH:48])[C:38]3[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][CH:39]=3)=[C:35]([CH:49]([CH3:51])[CH3:50])[CH:34]=[C:33]3[C:25]=2[C:26](=[O:52])[CH2:27][C:28]2([O:32]3)[CH2:31][CH2:30][CH2:29]2)=[CH:20][CH:19]=1>CO>[F:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[C:36]([C@H:37]([OH:48])[C:38]3[CH:43]=[CH:42][C:41]([C:44]([F:46])([F:47])[F:45])=[CH:40][CH:39]=3)=[C:35]([CH:49]([CH3:50])[CH3:51])[CH:34]=[C:33]3[C:25]=2[C@@H:26]([OH:52])[CH2:27][C:28]2([O:32]3)[CH2:31][CH2:30][CH2:29]2)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 580030305-(4-Fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Product 1

HCID 58003035HCID 58003035, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Under argon, 1.6 mg (0.011 mmol) of (1R,2S)-1-aminoindan-2-ol are dissolved in 1 ml of abs. tetrahydrofuran, 77 μl (0.43 mmol) of borane/N,N-diethylaniline complex are added and the mixture is stirred at room temperature for 30 min. After this time, 60 mg (0.108 mmol) of 5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropylspiro[chromen-2,1′-cyclobutan]-4(3H)-one (Example 52A), dissolved in 2 ml of abs. tetrahydrofuran, are added at room temperature over a period of 10 min, and the mixture is then stirred at room temperature for 18 h. 2 ml of methanol are added and the mixture is stirred for 15 min and then concentrated to dryness. The residue is taken up in ethyl acetate and washed twice with 1 N hydrochloric acid, twice with saturated sodium bicarbonate solution and twice with saturated sodium chloride solution. The organic phase is dried over sodium sulfate, filtered and concentrated. The crude product obtained is purified by preparative thick-layer chromatography (mobile phase: cyclohexane/ethyl acetate 4:1), resulting in the separation of the diastereomers.

Workup

  1. stirringthe mixture is then stirred at room temperature for 18 h
  2. stirringthe mixture is stirred for 15 min
  3. concentrationconcentrated to dryness
  4. washwashed twice with 1 N hydrochloric acid, twice with saturated sodium bicarbonate solution and twice with saturated sodium chloride solution
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4968833c00314417856733f315a2daf7
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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