Diisopropylethylamine → tert-butyl (3S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 660659Notes

Reaction equation

HRID 660659 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](O)=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[BH4-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C@H:17]([CH2:18][OH:19])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 664088(3S)-2-((tert-butoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 4311764Sodium borohydrideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 53811416tert-butyl (3S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester (1.0 g, 3.61 mmol) in THF (20 mL) is stirred at RT for 10 min. HATU (1.51 g, 3.97 mmol) is added and the suspension is allowed to stir at RT for 30 min. To the solution is added iPr2NEt (1.57 mL, 9.02 mmol) and the mixture is allowed to stir at RT for 18 h. NaBH4 is added (0.164 g, 4.33 mmol) then the mixture is quenched with MeOH (1 mL), extracted with EtOAc (2×30 mL), washed with 1N HCl (4×50 mL), saturated NaHCO3 (2×50 mL) and brine (2×50 mL). The organic layer is dried over Na2SO4 and concentrated. The residue is purified by column chromatography, eluting with a gradient of 20-50% EtOAc/hexane as eluent to afford the title compound.

Workup

  1. stirringto stir at RT for 18 h
  2. customthe mixture is quenched with MeOH (1 mL)
  3. extractionextracted with EtOAc (2×30 mL)
  4. washwashed with 1N HCl (4×50 mL), saturated NaHCO3 (2×50 mL) and brine (2×50 mL)
  5. dry with materialThe organic layer is dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue is purified by column chromatography
  8. washeluting with a gradient of 20-50% EtOAc/hexane as eluent

Sources & evidence

ORD record
ord-0d1eccdd99e040899ee87cbd948df569
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

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