Acetic Acid → (S)-4-(3-Hydroxymethyl-oxetan-3-ylmethyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

HRID 655545Notes

Reaction equation

HRID 655545 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][C:23]1([CH2:27][OH:28])[CH2:26][O:25][CH2:24]1.[B-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[CH2:13]([O:12][C:10]([N:6]1[CH2:7][CH2:8][N:21]([CH2:22][C:23]2([CH2:27][OH:28])[CH2:26][O:25][CH2:24]2)[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 11430Potassium CarbonateHCID 18706850[3-(Aminomethyl)oxetan-3-yl]methanolHCID 23676153Sodium bis(acetyloxy)boranuidyl acetateHCID 86638111(S)-2-[Benzyloxycarbonyl-(2-oxo-ethyl)-amino]-propionic acid methyl ester2×

Product 1

HCID 67079867(S)-4-(3-Hydroxymethyl-oxetan-3-ylmethyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl esterYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

A solution of (S)-2-[benzyloxycarbonyl-(2-oxo-ethyl)-amino]-propionic acid methyl ester (intermediate 27C; 258 mg, 0.92 mmol) in dichloromethane (1 mL) was added at room temperature to a suspension of (3-(aminomethyl)oxetan-3-yl)methanol (108 mg, 0.92 mmol), sodium triacetoxyborohyride (222 mg, 1.01 mmol) and acetic acid (111 mg, 1.85 mmol) in dichloromethane (1 mL). The reaction mixture was heated at 40° C. for 16 h, then partitioned between 1 M aq. sodium carbonate solution and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated. The residue was taken up in methanol (2 mL), then after addition of potassium carbonate (255 mg, 1.85 mmol) the suspension was stirred for 2 h. The reaction mixture was partitioned between sat. aq. ammonium chloride solution and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2; dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25) afforded the title compound (45 mg, 14%). Light yellow oil, MS (ISP)=349.3 (M+H)+.

Workup

  1. custompartitioned between 1 M aq. sodium carbonate solution and ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe reaction mixture was partitioned between sat. aq. ammonium chloride solution and ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated

Sources & evidence

ORD record
ord-ed45d48a780f4bceb4db849b43d7bb90
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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