Diisopropylethylamine → Di-tert-butyl dicarbonate

HRID 1715404Notes

Reaction equation

HRID 1715404 reaction equation
[C:1]([SiH2:5][O:6][C:7]([CH3:18])([CH3:17])[C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[Cl:16])[CH2:11][NH2:12])([CH3:4])([CH3:3])[CH3:2].[CH:19]1([CH:22]=O)[CH2:21][CH2:20]1.[BH4-].[Na+].CCN(C(C)C)C(C)C.[CH3:35][C:36]([O:39][C:40]([O:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[O:41])([CH3:38])[CH3:37]>CO.C(Cl)Cl>[C:36]([O:39][C:40](=[O:41])[N:12]([CH2:11][C:10]1[CH:13]=[CH:14][C:15]([Cl:16])=[C:8]([C:7]([CH3:18])([CH3:17])[O:6][SiH2:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:9]=1)[CH2:22][CH:19]1[CH2:20][CH2:21]1)([CH3:38])([CH3:37])[CH3:35].[CH3:38][C:36]([O:39][C:40]([O:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[O:41])([CH3:35])[CH3:37]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 123114CyclopropanecarboxaldehydeHCID 4311764Sodium borohydrideHCID 1373299203-(tert-Butyl-dimethyl-silanyloxymethyl)-4-chloro-benzylamine

Product 2

HCID 90495Di-tert-butyl dicarbonateYield 314.2%HCID 131728334HCID 131728334, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 3-(tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzylamine (2.00 g, 7.00 mmol) and cyclopropancarboxaldehyde (0.784 mL, 10.5 mmol) in MeOH (70 mL) was heated to reflux for 4 h. The mixture allowed to cool to rt. NaBH4 (397 mg, 10.5 mmol) was added in portion, and the mixture was stirred for 1 h at rt. The solvents were removed under reduced pressure, and the resulting oil was diluted with EtOAc. The resulting mixture was washed with aq. sat. NaHCO3 and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to yield the crude [3-(tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzyl]-cyclopropylmethyl-amine. This crude product was dissolved in CH2Cl2 (70 mL). DIPEA (3.60 mL, 21.0 mmol) and Boc2O (2.30 g, 10.5 mmol) were added. The mixture was stirred at rt for 2 h, and the mixture was diluted with CH2Cl2 (30 mL). The resulting mixture was washed with aq. 1M HCl, aq. sat. NaHCO3, and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane→EtOAc/heptane 10:90) yielded the title compound contaminated with Boc2O (3.60 g, quantitative yield). LC-MS: tR=1.25 min; ES+: 440.80.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 h
  3. customThe solvents were removed under reduced pressure
  4. additionthe resulting oil was diluted with EtOAc
  5. washThe resulting mixture was washed with aq. sat. NaHCO3 and brine
  6. dry with materiallayer was dried over MgSO4
  7. filtrationfiltered
  8. customthe solvents were removed under reduced pressure
  9. customto yield the crude [3-(tert-butyl-dimethyl-silanyloxymethyl)-4-chloro-benzyl]-cyclopropylmethyl-amine
  10. stirringThe mixture was stirred at rt for 2 h
  11. washThe resulting mixture was washed with aq. 1M HCl, aq. sat. NaHCO3, and brine
  12. dry with materiallayer was dried over MgSO4
  13. filtrationfiltered
  14. customthe solvents were removed under reduced pressure
  15. customPurification of the crude by FC (heptane→EtOAc/heptane 10:90)

Sources & evidence

ORD record
ord-7e5eb9f83a0845cd91562d7dc1d1fb2a
Source dataset
uspto-grants-2010_09
Patent number
US07799805B2

Reaction notes

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