4-Nitrobenzoic Acid → Di-tert-butyl (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-{[(4-nitrophenyl)carbonyl]oxy}bicyclo[3.1.0]hexane-2,6-dicarboxylate

HRID 2172989Notes

Reaction equation

HRID 2172989 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:20]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=1)([O-:22])=[O:21].[C:32]([O:36][C:37]([NH:39][C@@:40]1([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[C@H:45]([O:46][CH2:47][C:48]2[CH:53]=[CH:52][C:51]([Cl:54])=[C:50]([Cl:55])[CH:49]=2)[C@H:44](O)[C@@H:43]2[C@H:41]1[C@H:42]2[C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])=[O:38])([CH3:35])([CH3:34])[CH3:33].N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.C(OCC)C>[C:32]([O:36][C:37]([NH:39][C@@:40]1([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[C@H:45]([O:46][CH2:47][C:48]2[CH:53]=[CH:52][C:51]([Cl:54])=[C:50]([Cl:55])[CH:49]=2)[C@@H:44]([O:28][C:27]([C:26]2[CH:25]=[CH:24][C:23]([N+:20]([O-:22])=[O:21])=[CH:31][CH:30]=2)=[O:29])[C@@H:43]2[C@H:41]1[C@H:42]2[C:57]([O:59][C:60]([CH3:62])([CH3:61])[CH3:63])=[O:58])=[O:38])([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 86695972Di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate

Product 1

HCID 86695973Di-tert-butyl (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-{[(4-nitrophenyl)carbonyl]oxy}bicyclo[3.1.0]hexane-2,6-dicarboxylateYield 51%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Triphenylphosphine (12.66 g, 48.26 mmol) and 4-nitrobenzoic acid (8.19 g, 48.26 mmol) are added to di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate (14.20 g, 24.13 mmol) and tetrahydrofuran (241.28 mL, 2.97 moles) at room temperature. Cool the mixture in an ice bath. Diisopropyl azodicarboxylate (9.57 mL, 9.76 g, 48.26 mmol) in tetrahydrofuran (20 mL) is added and the reaction mixture is gradually warmed to room temperature overnight. Dilute with diethyl ether, and then wash with aqueous sodium carbonate. Extract the aqueous layer again with diethyl ether. Combine all ether extracts, wash with water, brine, dry over magnesium sulfate, and concentrate under reduced pressure to give a residue. The residue is purified by flash chromatography, eluting with 10-100% ethyl acetate in hexanes to give the title compound (9 g, 12.2 mmol, 51%): MS (m/z): 759 (M+1).

Workup

  1. temperatureCool the mixture in an ice bath
  2. washwash with aqueous sodium carbonate
  3. extractionExtract the aqueous layer again with diethyl ether
  4. washwash with water, brine
  5. dry with materialdry over magnesium sulfate
  6. concentrationconcentrate under reduced pressure
  7. customto give a residue
  8. customThe residue is purified by flash chromatography
  9. washeluting with 10-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-1eba926459354bfc9448b07d66cfd221
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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