Citric Acid → HCID 69492169, compound

HRID 1768145Notes

Reaction equation

HRID 1768145 reaction equation
[C:1]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH2:11][S:12][CH3:13])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.Cl.[CH2:42]([O:49][C:50]1[CH:56]=[CH:55][C:53]([NH2:54])=[CH:52][CH:51]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(N(C(C)C)C(C)C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[C:4]([O:3][C:1](=[O:2])[NH:8][C@H:9]([C:14](=[O:16])[NH:54][C:53]1[CH:52]=[CH:51][C:50]([O:49][CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)=[CH:56][CH:55]=1)[CH2:10][CH2:11][S:12][CH3:13])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 89857Boc-L-methionineHCID 27238314-Benzyloxyaniline hydrochlorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 69492169HCID 69492169, compoundYield 82.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.57 g (2.3 mmol) of (S)-Boc-methionine in 5 ml of dichloromethane is treated at RT consecutively with 0.87 g (2.3 mmol) of O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (HBTU), 0.50 g (2.1 mmol) of 4-benzyloxyaniline hydrochloride and 0.98 ml (5.7 mmol) of N-ethyl-diisopropylamine. The reaction mixture is stirred during 1 h at RT. For the working-up, the reaction mixture is diluted with dichloromethane and treated with 20 ml of an aqueous solution of citric acid (10%). The aqueous phase is re-extracted with dichloromethane, the organic phases combined, dried over sodium sulfate and evaporated under reduced pressure. For purification, the crude material obtained is chromatographed on silica gel using a 3:1 mixture of n-hexane and ethyl acetate as the eluent. There are obtained 0.74 g (82.5% of theory) of (S)-[1-(4-benzyloxy-phenylcarbamoyl)-3-methylsulfanyl-propyl]-carbamic acid tert-butyl ester as a white solid. MS: m/e=431 (M+H)+.

Workup

  1. extractionThe aqueous phase is re-extracted with dichloromethane
  2. dry with materialdried over sodium sulfate
  3. customevaporated under reduced pressure
  4. customFor purification
  5. customthe crude material obtained
  6. customis chromatographed on silica gel using
  7. additiona 3:1 mixture of n-hexane and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-14bd2decb69d4c3392f6e41df3e965d4
Source dataset
uspto-grants-2007_06
Patent number
US07235581B2

Reaction notes

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