Diisopropylethylamine → 1-[(1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-(3-hydroxy-3-methyl-butyl)-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl]-2-(2-chloro-5-methoxy-phenyl)ethanone

HRID 1854566Notes

Reaction equation

HRID 1854566 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[CH2:20][CH2:21][C:22]([CH3:25])([OH:24])[CH3:23])[C@H:12]([CH3:26])[NH:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][C:38]=1[CH2:45][C:46](O)=[O:47].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>ClCCl>[Si:1]([O:8][CH2:9][C@H:10]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[CH2:20][CH2:21][C:22]([OH:24])([CH3:25])[CH3:23])[C@H:12]([CH3:26])[N:11]1[C:46](=[O:47])[CH2:45][C:38]1[CH:39]=[C:40]([O:43][CH3:44])[CH:41]=[CH:42][C:37]=1[Cl:36])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 153659582-Chloro-5-methoxybenzeneacetic acidHCID 1236252274-((1S,3R)-3-(((tert-Butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl)-2-methylbutan-2-ol

Product 1

HCID 1240085001-[(1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-(3-hydroxy-3-methyl-butyl)-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl]-2-(2-chloro-5-methoxy-phenyl)ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Dissolve 4-[(1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl]-2-methyl-butan-2-ol (0.36 g, 0.95 mol in dichloromethane (9.5 mL). Add diisopropylethylamine (499 μL, 2.86 mmol). Add 2-(2-chloro-5-methoxy-phenyl)acetic acid (229.5 mg, 1.14 mmol). Add O-(7-aza-1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (561 mg, 1.40 mmol) and stir at ambient temperature overnight. Dilute the reaction mixture with dichloromethane and wash with water and brine, dry over sodium sulfate, filter, and concentrate under reduced pressure to give a brown oil. Purify the residue by silica gel chromatography, eluting with acetone: hexanes (gradient, 0-20%) to give the title compound as an opaque oil (0.46 g, 0.82 mmol). MS (m/z): 560.2 (M+1).

Workup

  1. washwash with water and brine
  2. dry with materialdry over sodium sulfate
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure
  5. customto give a brown oil
  6. customPurify the residue by silica gel chromatography
  7. washeluting with acetone

Sources & evidence

ORD record
ord-e2599a92149b400d922a69857e593021
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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