Formaldehyde → Benzyl(2R,5S)-2-[bis(tert-butoxycarbonyl)amino]-5-(2,3-difluorophenyl)-7-hydroxy-6-nitroheptanoate

HRID 20169Notes

Reaction equation

HRID 20169 reaction equation
[C:1]([O:5][C:6]([N:8]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C@@H:9]([C:25]([O-:27])=[O:26])[CH2:10][CH2:11][C@@H:12]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[F:24])[CH2:13][N+:14]([O-:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)C(N(C)C)=N.[CH2:43]=[O:44]>C(#N)C.C([O-])(O)=O.[Na+]>[C:31]([O:30][C:28]([N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C@H:9]([CH2:10][CH2:11][C@@H:12]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=1[F:24])[CH:13]([N+:14]([O-:16])=[O:15])[CH2:43][OH:44])[C:25]([O:27][CH2:12][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:26])=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 712Formaldehyde2×HCID 664601,1,3,3-TetramethylguanidineHCID 66938815(5S)-N,N-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-6-nitro-D-norleucinate

Product 1

HCID 66939304Benzyl(2R,5S)-2-[bis(tert-butoxycarbonyl)amino]-5-(2,3-difluorophenyl)-7-hydroxy-6-nitroheptanoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (5S)—N,N-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-6-nitro-D-norleucinate (2.30 g, 3.975 mmol) and 1,1,3,3-tetramethylguanidine (46 mg, 0.40 mmol) in acetonitrile (20 mL) was added formaldehyde (0.15 mL, 37% aqueous solution). After stirring for 60 min, more formaldehyde (0.050 mL, 37% aqueous solution) was added. After stirring for an additional 60 min the mixture was diluted with saturated aqueous NaHCO3 and extracted with CH2Cl2 (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated to give a residue that was purified by silica gel chromatography (25%→75% ethyl acetate/hexanes) to give the title compound (1.44 g,). MS 409.1 (M+1-2Boc).

Workup

  1. stirringAfter stirring for an additional 60 min the mixture
  2. extractionextracted with CH2Cl2 (3×)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customwas purified by silica gel chromatography (25%→75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-25e48a103cd243de96fabe91da39ff53
Source dataset
uspto-grants-2010_06
Patent number
US07745427B2

Reaction notes

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