Aluminium lithium hydride → (R)-[1-(4-Benzyloxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 852866Notes

Reaction equation

HRID 852866 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([O:11][C:12](=[O:36])[NH:13][C@@H:14]([C:30](=[O:35])N(OC)C)[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:18][CH:17]=1)([CH3:10])([CH3:9])[CH3:8]>C1COCC1>[C:7]([O:11][C:12](=[O:36])[NH:13][C@H:14]([CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:20][CH:21]=1)[CH:30]=[O:35])([CH3:10])([CH3:8])[CH3:9]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 51356829(R)-[2-(4-Benzyloxy-phenyl)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 51356831(R)-[1-(4-Benzyloxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl esterYield 99.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LiAlH4 (916 mg, 24.1 mmol) was added cautiously and portionwise during 15 min to a stirred solution of (R)-[2-(4-Benzyloxy-phenyl)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester (10.00 g, 24.1 mmol) in THF (150 mL) at 0° C. under an atmosphere of argon. The ice-bath was removed and the mixture was stirred for 1 h, then poured onto a mixture of ice and KHSO4 (1M aqueous). When the ice had melted the product was extracted into EtOAc. The combined extracts were washed with brine then dried (Na2SO4) and evaporated to give the aldehyde as pale yellow crystals (8.51 g, 99%), mp 100.3-101.7° C. (lit. mp 98-99° C.).[W. J. Thompson et al, Tetrahedron Lett., 1990, 31, 6819] 1H NMR (CDCl3) δ 9.63 (1H, s, CHO), 7.45-7.33 (5H, m), 7.09 (2H, d, J=8.7 Hz), 6.92 (2H, d, J=8.6 Hz), 5.05 (2H, s, OCH2Ph), 4.40 (1H, br s, Hα), 3.07 (2H, d, J=6.7 Hz, Hβ,β), 1.44 (9H, s, CMe3). 13C NMR (CDCl3) δ 199.6, 156.4, 144.4, 136.8, 130.4, 128.6, 128.5, 128.0, 127.9, 127.5, 115.1, 80.9, 70.0, 46.0, 34.6, 28.3.

Workup

  1. customThe ice-bath was removed
  2. additionpoured onto a mixture of ice and KHSO4 (1M aqueous)
  3. extractionwas extracted into EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialthen dried (Na2SO4)
  6. customevaporated

Sources & evidence

ORD record
ord-21e614bfadac4ec8bb87825bc9b765ca
Source dataset
uspto-grants-2007_08
Patent number
US07253194B2

Reaction notes

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