HCID 9969778, compound → HCID 22720299, compound

HRID 1582453Notes

Reaction equation

HRID 1582453 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([N:14]1[CH2:34][CH2:33][C:18]2=[C:19]([C:26](=[O:32])[C:27](OCC)=[O:28])[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[N:17]2[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C1COCC1>[CH2:7]([N:14]1[CH2:34][CH2:33][C:18]2=[C:19]([CH:26]([OH:32])[CH2:27][OH:28])[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[N:17]2[CH2:16][CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 9969778HCID 9969778, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 22720299HCID 22720299, compoundYield 168.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

(Chart D, Step 2): A dry round bottom flask is charged with THF (100 mL) and 1M LAH in THF (65.13 mL, 65.13 mmol). A solution of ethyl 2-(3-benzyl-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)-2-oxoacetate (6.13 g, 16.28 mmol) in THF (75 mL) is slowly added to the reaction via syringe. The addition is exothermic. The reaction mixture is heated to reflux for 5 hours then reaction is quenched with a very slow and sequential addition of a) 2.47 mL H2O, b) 2.22 mL of 5N aq. NaOH, and c) 8.64 mL H2O. The resulting heterogeneous solution is stirred vigorously with excess ethyl acetate for one hour and filtered through a pad of celite. The filtrate is concentrated to give 9.23 g of 1-(3-benzyl-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)-1,2-ethanediol as a crude yellow solid. A 2 L round bottom is charged with a solution of the crude diol in dichloromethane (541 mL). A semi-dropwise addition of TFA (14.46 mL, 188 mmol) is followed by the slow addition of triethylsilane (9.1 mL, 57 mmol) and the mixture is first refluxed for two hours, then stirred at ambient temperature for 18 hours. The resulting brown solution is concentrated in vacuo, diluted with dichloromethane, basified with sat. aq. Na2CO3 and vigorously stirred while cooling to 10° C. The mixture is transferred to a round bottom, volatiles are removed in vacuo at 50° C. The residue is partitioned between water and dichloromethane. The organics are combined, dried with Na2SO4, filtered and concentrated to give 5.57 g of an orange oil. Purification of the crude on silica gel using a gradient of 35%-50% ethyl acetate/heptane as the eluent gives 3.52 g of 2-(3-benzyl-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indol-11-yl)-1-ethanol as a tan oil. IR (liq.) 2933, 2873, 2816, 1469, 1453, 1427, 1376, 1364, 1347, 1325, 1185, 1046, 1015, 733, 699 cm−1.

Workup

  1. additionThe addition
  2. temperatureThe reaction mixture is heated
  3. temperatureto reflux for 5 hours
  4. customreaction
  5. customis quenched with a very slow and
  6. additionsequential addition of a) 2.47 mL H2O, b) 2.22 mL of 5N aq. NaOH, and c) 8.64 mL H2O
  7. filtrationfiltered through a pad of celite
  8. concentrationThe filtrate is concentrated

Sources & evidence

ORD record
ord-e93c83f06fee4f3b9a98faab931fbd3b
Source dataset
uspto-grants-2004_05
Patent number
US06734301B2

Reaction notes

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