Borane → HCID 67517810, compound

HRID 61396Notes

Reaction equation

HRID 61396 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:17]([C:18](O)=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][C:12]([Cl:21])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B>C1COCC1>[Cl:21][C:12]1[CH:11]=[C:10]2[C:15]([CH2:16][CH:17]([CH2:18][OH:19])[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]2)=[CH:14][CH:13]=1

Participants

4

Reactant 2

HCID 6331BoraneHCID 67513180HCID 67513180, compound

Product 1

HCID 67517810HCID 67517810, compoundYield 76.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

While under nitrogen, a flame-dried flask was charged with 2-(tert-butoxycarbonyl)-7-chloro-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (400 mg, 1.28 mmol) and anhydrous THF (2.5 mL), cooled in an ice-saturated aqueous sodium chloride bath and carefully treated with a solution of borane in THF (1 M, 2.63 mL, 2.63 mmol). The resulting mixture was stirred at 0° C. for ˜1.5 h and then at room temperature overnight. The mixture was then cooled in an ice-water bath, quenched slowly by the dropwise addition of water until most gas evolution ceased, diluted with additional water (15 mL) and extracted with ethyl acetate (2×25 mL). The combined organic phase was washed with saturated aqueous NaHCO3 (10 mL), water (10 mL) and saturated aqueous sodium chloride (10 mL), dried over Na2SO4 and concentrated under reduced. Purification by silica gel chromatography (40 g column, 10-20% ethyl acetate in methylene chloride) gave tert-butyl 7-chloro-3-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (292 mg, 76%) as a clear gum. 1H NMR (DMSO-d6, 400 MHz) δ 7.29 (m, 1 H), 7.20 (m, 2 H), 4.81 (m, 1 H), 4.64 (d, J=17 Hz, 1 H), 4.20 (bm, 2 H), 3.30 (m, 1 H), 3.12 (m, 1 H), 2.84 (m, 2 H), 1.43 (s, 9 H).

Workup

  1. temperaturecooled in an ice-saturated aqueous sodium chloride bath
  2. customat room temperature
  3. customovernight
  4. temperatureThe mixture was then cooled in an ice-water bath
  5. customquenched slowly by the dropwise addition of water until most gas evolution
  6. additiondiluted with additional water (15 mL)
  7. extractionextracted with ethyl acetate (2×25 mL)
  8. washThe combined organic phase was washed with saturated aqueous NaHCO3 (10 mL), water (10 mL) and saturated aqueous sodium chloride (10 mL)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced
  11. customPurification by silica gel chromatography (40 g column, 10-20% ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-90f58d82106844c9b315d95e3b3be28f
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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