Aluminium lithium hydride → HCID 21341515, compound

HRID 2304864Notes

Reaction equation

HRID 2304864 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].COCN[C:11](=[O:29])[C@@H:12]([CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]>O1CCCC1>[C:14]([NH:13][C@@H:12]([CH:11]=[O:29])[CH2:21][CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 21341520HCID 21341520, compound

Product 1

HCID 21341515HCID 21341515, compoundYield 96.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-35 °C

Procedure

A cold (−40° C.) solution of lithium aluminum hydride (25.2 mL of a 1M solution) in tetrahydrofuran (165 mL), under nitrogen, is treated with a solution of N-Boc-D-homophenylalanine methoxymethylamide (6.76 g) in tetrahydrofuran (20 mL) at such a rate as to keep the temperature between −36 to −38° C. After the addition, the temperature is allowed to rise to 7° C. after which the reaction mixture is cooled to −35° C. The mixture is quenched with 2.75 M KHSO4 solution and the mixture is stirred for 1 h while warming to 25° C. The aqueous layer is separated and extracted thrice with ether. The combined organics are washed successively thrice with 10% citric acid, water, saturated bicarbonate and brine, dried (MgSO4) and concentrated. The viscous clear residue solidifies under vacuum to give the title compound (5.32 g): 1H NMR (400 MHz, CDCl3) δ 1.47 (s, 9H), 1.88 (m, 1H), 2.22 (m, 1H), 2.71 (t, J=7.6 Hz, 2H), 4.24 (m, 1H), 5.18 (bd, 1H, NH), 7.20 (m, 3H), 7.27 (m, 2H), and 9.54 (s, 1H).

Workup

  1. custombetween −36 to −38° C
  2. additionAfter the addition
  3. customto rise to 7° C.
  4. customThe mixture is quenched with 2.75 M KHSO4 solution
  5. temperaturewhile warming to 25° C
  6. customThe aqueous layer is separated
  7. extractionextracted thrice with ether
  8. washThe combined organics are washed successively thrice with 10% citric acid, water, saturated bicarbonate and brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-a2197792bab04cf6b79a911256328615
Source dataset
uspto-grants-2002_08
Patent number
US06436980B1

Reaction notes

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