Triethylamine → (R)-N-Boc-1,2,3,4-tetrahydro-3-isoquinolinylmethanol

HRID 601699Notes

Reaction equation

HRID 601699 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].C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+]>C1COCC1.CO>[OH:19][CH2:18][C@H:17]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 688607(3R)-2-[(tert-butoxy)carbonyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 4311764Sodium borohydride

Product 1

HCID 60068810(R)-N-Boc-1,2,3,4-tetrahydro-3-isoquinolinylmethanolYield 91%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the compound of Step A (1) ((R)-2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, 6.3 g, 23 mmol) in THF (200 mL) was added triethylamine (36.5 mmol) followed by ethyl chloroformate (27.3 mmol). The mixture was stirred at rt for 2 h. NaBH4 (91.0 mmol) was then added and the mixture was stirred for 10 min. To the resulting mixture was added MeOH (40 ml) very slowly. When the addition was complete, the mixture was stirred for 3 h. The reaction was then concentrated in vacuo and the residue was partitioned between 1N NaOH and ethyl acetate (600 mL). The organic phase was washed with H2O, dried (Na2SO4), and concentrated in vacuo to give 5.5 g (91%) of the title compound: 1H NMR (CDCl3, 500 MHz) δ 1.49 (9H, s), 3.02 (1H, dd, J=5, 15 Hz), 3.50 (2H, brd s), 3.61 (1H, d, J=10 Hz), 4.30 (1H, d, J=15 Hz), 4.44-4.52 (1H, m), 4.67-4.76 (1H, m), 7.09-7.18 (4H, m). MS (ESI) (M+H)+ 264.19.

Workup

  1. stirringthe mixture was stirred for 10 min
  2. additionWhen the addition
  3. stirringthe mixture was stirred for 3 h
  4. concentrationThe reaction was then concentrated in vacuo
  5. customthe residue was partitioned between 1N NaOH and ethyl acetate (600 mL)
  6. washThe organic phase was washed with H2O
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-22f2f3edf2bc470d8dc8b3e3530a3341
Source dataset
uspto-grants-2011_03
Patent number
US07902218B2

Reaction notes

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