Ethyldiphenylphosphine → tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 579535Notes

Reaction equation

HRID 579535 reaction equation
C1(P(CC)C2C=CC=CC=2)C=CC=CC=1.[CH3:16][C:17]1([CH3:24])[C:21]([CH3:23])([CH3:22])[O:20][BH:19][O:18]1.[C:25]([NH:28][C:29]([C:54](=[O:60])[NH:55][C:56]([CH3:59])([CH3:58])[CH3:57])([CH2:49][CH2:50][CH2:51][CH:52]=C)[CH2:30][CH2:31][CH:32]1[CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][N:33]1[C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])(=[O:27])[CH3:26]>ClCCl>[C:25]([NH:28][C:29]([C:54](=[O:60])[NH:55][C:56]([CH3:59])([CH3:58])[CH3:57])([CH2:49][CH2:50][CH2:51][CH2:52][B:19]1[O:20][C:21]([CH3:23])([CH3:22])[C:17]([CH3:24])([CH3:16])[O:18]1)[CH2:30][CH2:31][CH:32]1[CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][N:33]1[C:42]([O:44][C:45]([CH3:46])([CH3:47])[CH3:48])=[O:43])(=[O:27])[CH3:26]

Participants

5

Reactant 3

HCID 69082EthyldiphenylphosphineHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 66833614tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)oct-7-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 66833409tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

While under an atmosphere of argon, a solution of bis(1,5-dicyclooctadiene)diiridium(I) dichloride (54 mg, 3% mol), diphenylphosphinoethane (64 mg, 6% mol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 mL, 10.7 mmol) in dry dichloromethane (20 mL) was cooled to 0° C. A second solution of tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)oct-7-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.5 g, 2.67 mmol) in dry dichloromethane (20 mL) was added in one portion. After 4 h LCMS indicated all the starting olefin was consumed and the reaction was washed successively with water, sat'd aq sodium chloride, dried over MgSO4, filtered and concentrated. Purification by flash chromatography (20-35% ethyl acetate in hexanes) gave tert-butyl 3-(3-acetamido-3-(tert-butylcarbamoyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)heptyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate as a yellow oil (1.5 g, 93%). ESI MS found for C34H56BN3O6 m/z [614.7 (M+1), 633.7 (M+23)].

Workup

  1. customall the starting olefin was consumed
  2. washthe reaction was washed successively with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography (20-35% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-22e97bf785b24a649c4e2ce438dd3f1f
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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