Water → HCID 69819839, compound

HRID 1006358Notes

Reaction equation

HRID 1006358 reaction equation
[ClH:1].Cl.[CH:3]([C@H:16]1[N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[CH2:19][N:18]([CH2:25][C:26]2[CH:31]=[C:30](Br)[CH:29]=[CH:28][C:27]=2[O:33][CH3:34])[CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.O>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[ClH:1].[CH:3]([C@H:16]1[N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[CH2:19][N:18]([CH2:25][C:26]2[CH:31]=[C:30]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:29]=[CH:28][C:27]=2[O:33][CH3:34])[CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 3

HCID 962WaterHCID 66827Phenylboronic AcidHCID 69819834HCID 69819834, compound

Product 1

HCID 69819839HCID 69819839, compoundYield 164.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
85 °C

Procedure

(4R,8aS)-4-Benzhydryl-2-(2-methoxy-5-bromobenzyl)octahydropyrrolo[1,2-a]pyrazine dihydrochloride (29.8 mg) was dissolved in a mixture of 1,2-dimethoxyethane (0.5 ml) and 2M aqueous sodium carbonate (0.16 ml). Then phenylboronic acid (9.01 mg) and tetrakis(triphenylphosphine)palladium (6.1 mg) were added to the solution at room temperature. The whole was stirred for 2 hours at 85° C. The reaction mixture was poured into water, extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was purified by preparative TLC (0.5 mm) with a mixture of dichloromethane and methanol (15:1) as an eluent, and treated with 4N hydrogen chloride in ethyl acetate to give (4R,8aS)-4-benzhydryl-2-[(4-methoxy-[1,1′-biphenyl]-3-yl)methyl]octahydropyrrolo[1,2-a]pyrazine dihydrochloride (24.4 mg) as a brownish power.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe resulting residue was purified by preparative TLC (0.5 mm) with a mixture of dichloromethane and methanol (15:1) as an eluent
  6. additiontreated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-48b07ced20824e3c9a9b95872dd96dfc
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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