Tetrahydrofuran → HCID 67407238, compound

HRID 2066965Notes

Reaction equation

HRID 2066965 reaction equation
[NH2:1][CH2:2][CH:3]1[C:8]2([C:13]3[NH:14][C:15]4[C:20]([C:12]=3[CH2:11][CH2:10][O:9]2)=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH2:7][CH2:6][C:5]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)([N:21]([CH3:23])[CH3:22])[CH2:4]1.CCN([CH:37]([CH3:39])[CH3:38])C(C)C.[C:40](Cl)(=[O:49])[CH:41]=[CH:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.[OH-].[Na+].O1C[CH2:56][CH2:55][CH2:54]1>O>[CH3:22][N:21]([CH3:23])[C:5]1([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)[CH2:6][CH2:7][C:8]2([C:13]3[NH:14][C:15]4[C:20]([C:12]=3[CH2:11][CH2:10][O:9]2)=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH:3]([CH2:2][NH:1][C:40](=[O:49])[CH:41]=[CH:42][C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([C:38]3[CH:37]=[CH:39][CH:56]=[CH:55][CH:54]=3)[CH:44]=2)[CH2:4]1

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 660233-Phenylprop-2-enoyl chlorideHCID 81531DiisopropylethylamineHCID 67407210HCID 67407210, compound

Product 1

HCID 67407238HCID 67407238, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-(aminomethyl)-4-(3-fluorophenyl)-N,N-dimethyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4-b]indole]-4-amine (130 mg, 0.31 mmol) was dissolved in absolute tetrahydrofuran (20 ml) with argon. Hünig's base (0.1 ml, 0.63 mmol) and cinnamic acid chloride (105 mg, 0.63 mmol) dissolved in absolute tetrahydrofuran (8 ml) were added one after the other to the clear solution at room temperature. After a reaction time of 45 min, the batch was mixed with water (10 ml) and 2 N sodium hydroxide solution (10 ml) and stirred for 1 h. For work up tetrahydrofuran was distilled off completely. The aqueous mixture was extracted with dichloromethane (3×20 ml). The combined organic extracts were washed once again with water (20 ml), dried over Na2SO4 and concentrated to low volume. The raw product (247 mg) was separated by chromatography [silica gel 60 (30 g); ethyl acetate/cyclohexane 5:1 (600 ml)]. One of four possible diastereoisomers was obtained as white solid with a yield of 108 mg (65%) and with a melting point of 134-140° C.

Workup

  1. additionwere added one after the other to the clear solution at room temperature
  2. distillationFor work up tetrahydrofuran was distilled off completely
  3. extractionThe aqueous mixture was extracted with dichloromethane (3×20 ml)
  4. washThe combined organic extracts were washed once again with water (20 ml)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to low volume
  7. customThe raw product (247 mg) was separated by chromatography [silica gel 60 (30 g); ethyl acetate/cyclohexane 5:1 (600 ml)]
  8. customOne of four possible diastereoisomers was obtained as white solid with a yield of 108 mg (65%) and with a melting point of 134-140° C.

Sources & evidence

ORD record
ord-309e7cd3dfd3464596bdc98df94b01f4
Source dataset
uspto-grants-2012_10
Patent number
US08293758B2

Reaction notes

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