Acetic Acid → (S)-4-(4-Hydroxy-butyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

HRID 655541Notes

Reaction equation

HRID 655541 reaction equation
CO[C:3](=[O:20])[C@@H:4]([N:6]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[CH2:7][CH:8]=O)[CH3:5].[NH2:21][CH2:22][CH2:23][CH2:24][CH2:25][OH:26].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>ClCCl>[CH2:13]([O:12][C:10]([N:6]1[CH2:7][CH2:8][N:21]([CH2:22][CH2:23][CH2:24][CH2:25][OH:26])[C:3](=[O:20])[C@@H:4]1[CH3:5])=[O:11])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 258684-Amino-1-butanolHCID 5049666Sodium triacetoxyborohydrideHCID 86638111(S)-2-[Benzyloxycarbonyl-(2-oxo-ethyl)-amino]-propionic acid methyl ester

Product 1

HCID 67079818(S)-4-(4-Hydroxy-butyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-2-[benzyloxycarbonyl-(2-oxo-ethyl)-amino]-propionic acid methyl ester (24.3 g, 80 mmol) in dichloromethane (130 mL) was added at room temperature over 15 min to a suspension of 4-amino-1-butanol (7.12 g, 80 mmol), acetic acid (9.6 g, 0.16 mol), and sodium triacetoxyborohydride (25.4 g, 0.12 mol), then after 16 h triethylamine (16.2 g, 0.16 mol) was added, and the reaction mixture was concentrated under vacuum. The residue was partitioned between 2 M aq. sodium carbonate solution and ethyl acetate. The organic layer was dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; dichloromethane, then dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25) afforded the title compound (16.8 g, 66%). Yellow oil, MS (ISP)=321.2 (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated under vacuum
  2. customThe residue was partitioned between 2 M aq. sodium carbonate solution and ethyl acetate
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-b37f8927f5da450b8a9891e6cf63d7ba
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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