Acetic Acid → (2R)-3-benzyloxy-2-(N-(4-fluorobenzyl)amino)propanoic acid methyl ester

HRID 489194

Reaction equation

HRID 489194 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C@H:4]([NH2:14])[CH2:5][O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(O)(=O)C.[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][CH:22]=1.C([BH3-])#N.[Na+]>CO.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:15])[C@H:4]([NH:14][CH2:25][C:24]1[CH:27]=[CH:28][C:21]([F:20])=[CH:22][CH:23]=1)[CH2:5][O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 680234-FluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 13635389(2R)-3-benzyloxy-2-aminopropanoic acid methyl ester

Product 1

HCID 54459095(2R)-3-benzyloxy-2-(N-(4-fluorobenzyl)amino)propanoic acid methyl esterYield 60%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (2R)-3-benzyloxy-2-aminopropanoic acid methyl ester (19 g, 78 mmol) in methanol (350 mL) under N2 was cooled to 0° C. and acetic acid (2 g, pH 2) was added, followed by the addition of 4-fluorobenzaldehyde, a compound of formula (N) (12.5 mL, 117 mmol) and sodium cyanoborohydride (7.3 g, 117 mmol) and 3 Å molecular sieves (15 g). The resulting mixture was stirred at ambient temperature for 3 hours, then filtered through Celite (MeOH). The filtrate was concentrated in vacuo to afford a clear liquid. This was taken up in ethyl acetate and washed sequentially with 10% aqueous Na2CO3 solution, water, then brine. The organic phase was then dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel afforded 14.7 g (60% yield) of (2R)-3-benzyloxy-2-(N-(4-fluorobenzyl)amino)propanoic acid methyl ester, a compound of formula (O), as a clear, colorless oil; NMR (CDCl3) 7.4-7.2 (m, 7), 7.0 (dd, 2), 4.5 (d, 2), 3.9-3.5 (m, 8) ppm, MS (LSIMS) 317.

Workup

  1. filtrationfiltered through Celite (MeOH)
  2. concentrationThe filtrate was concentrated in vacuo
  3. customto afford a clear liquid
  4. washwashed sequentially with 10% aqueous Na2CO3 solution, water
  5. dry with materialThe organic phase was then dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-73e681f1ebb84499896ac0a9ba05ef94
Source dataset
uspto-grants-2005_12
Patent number
US06977258B2

Linked notes

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