[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol → (R)-methyl 2-(tert-butoxycarbonylamino)-2-(2-((S)-3-(hydroxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate

HRID 579481Notes

Reaction equation

HRID 579481 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]([CH2:27][CH:28]=O)([CH2:14][CH2:15][CH2:16][CH2:17][B:18]1[O:22][C:21]([CH3:24])([CH3:23])[C:20]([CH3:26])([CH3:25])[O:19]1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:30]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:33][C@@H:32]([CH2:40][OH:41])[NH:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6]([NH:8][C@@:9]([CH2:27][CH2:28][N:31]1[C@H:32]([CH2:40][OH:41])[CH2:33][C:34]2[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:30]1)([CH2:14][CH2:15][CH2:16][CH2:17][B:18]1[O:19][C:20]([CH3:26])([CH3:25])[C:21]([CH3:24])([CH3:23])[O:22]1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 776757[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanolHCID 5049666Sodium triacetoxyborohydrideHCID 71600280(R)-methyl 2-(tert-butoxycarbonylamino)-2-(2-oxoethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate

Product 1

HCID 66833499(R)-methyl 2-(tert-butoxycarbonylamino)-2-(2-((S)-3-(hydroxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoateYield 93.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of (R)-methyl 2-(tert-butoxycarbonylamino)-2-(2-oxoethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate (0.148 g, 0.358 mmol, 1.0 equiv.) and (S)-(1,2,3,4-tetrahydroisoquinolin-3-yl)methanol (0.088 g, 0.54 mmol, 1.5 equiv.) in 1,2-dichloroethane (0.34 mL, 0.5 M) was treated with sodium triacetoxyborohydride (0.19 g, 0.90 mmol, 2.5 equiv) in one portion. After stirring for 1.5 h, the reaction mixture was quenched with saturated aqueous NaHCO3 (1 mL) and stirred for an additional 5 min. The resulting mixture was added to a separatory funnel, diluted with saturated aqueous NaCl (5 mL) and extracted with dichloromethane (2×10 mL). The organic layer was dried over MgSO4, filtered and concentration under reduced pressure. Purification by flash column chromatography eluting with 5% methanol in chloroform gave (R)-methyl 2-(tert-butoxycarbonylamino)-2-(2-((S)-3-(hydroxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate as a pale yellow oil (0.187 g, 93%). Rf 0.52 (10% methanol in dichloromethane); 1H NMR (CDCl3, 300 MHz) δ 7.15-7.08 (m, 2H), 7.07-6.98 (m, 2H), 5.90 (s, 1H), 3.78 (d, J=16.2 Hz, 1H), 3.70 (s, 3H), 3.60-3.47 (m, 2H), 3.04-2.93 (m, 1H), 2.92-2.82 (m, 1H), 2.71-2.60 (m, 1H), 2.56-2.38 (m, 2H), 2.37-2.23 (m, 1H), 2.21-2.10 (m, 1H), 1.77-1.63 (m, 1H), 1.42 (s, 9H), 1.43-1.26 (m, 3H), 1.23 (s, 12H), 1.22-1.16 (m, 1H), 0.99-0.82 (m, 2H), 0.74 (t, J=7.5 Hz, 2H); ESI-LCMS m/z calcd for C30H49BN2O7: expected 560.4. found 561.4 (M+H)+.

Workup

  1. customthe reaction mixture was quenched with saturated aqueous NaHCO3 (1 mL)
  2. stirringstirred for an additional 5 min
  3. additionThe resulting mixture was added to a separatory funnel
  4. additiondiluted with saturated aqueous NaCl (5 mL)
  5. extractionextracted with dichloromethane (2×10 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentration under reduced pressure
  9. customPurification by flash column chromatography
  10. washeluting with 5% methanol in chloroform

Sources & evidence

ORD record
ord-f04a63e1c6484f84bc1ce2e1f2f2549e
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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