Formic Acid → N-(tert-Butoxycarbonyl)-O-{[(4R,7S)-4-carbamoyl-13,13-dimethyl-6,11-dioxo-1,1,1-triphenyl-12-oxa-2-thia-5,10-diazatetradecan-7-yl]carbamoyl}-L-tyrosine

HRID 630677Notes

Reaction equation

HRID 630677 reaction equation
C([O:4][C:5](=[O:65])[C@H:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23](=[O:64])[NH:24][C@@H:25]([CH2:54][CH2:55][NH:56][C:57](=[O:63])[O:58][C:59]([CH3:62])([CH3:61])[CH3:60])[C:26](=[O:53])[NH:27][C@H:28]([C:50](=[O:52])[NH2:51])[CH2:29][S:30][C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:18][CH:17]=1)[NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])C=C.C(N(CC)CC)C.C(O)=O>O1CCCC1.O>[C:11]([O:10][C:8]([NH:7][C@H:6]([C:5]([OH:65])=[O:4])[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][C:23](=[O:64])[NH:24][C@@H:25]([CH2:54][CH2:55][NH:56][C:57](=[O:63])[O:58][C:59]([CH3:60])([CH3:62])[CH3:61])[C:26](=[O:53])[NH:27][C@H:28]([C:50](=[O:52])[NH2:51])[CH2:29][S:30][C:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:20][CH:21]=1)=[O:9])([CH3:12])([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 89555014Allyl-N-(tert-butoxycarbonyl)-O-{[(4R,7S)-4-carbamoyl-13,13-dimethyl-6,11-dioxo-1,1,1-triphenyl-12-oxa-2-thia-5,10-diazatetradecan-7-yl]carbamoyl}-L-tyrosinate

Product 1

HCID 71557416N-(tert-Butoxycarbonyl)-O-{[(4R,7S)-4-carbamoyl-13,13-dimethyl-6,11-dioxo-1,1,1-triphenyl-12-oxa-2-thia-5,10-diazatetradecan-7-yl]carbamoyl}-L-tyrosine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

4.91 g (5.40 mmol) of the compound from example 14A was dissolved in approx. 110 ml tetrahydrofuran. 3.8 ml (27 mmol) Triethylamine, 1.02 ml (27 mmol) formic acid and 0.62 g (0.54 mmol) tetrakis(triphenylphosphin)palladium(0) were added. The reaction mixture was stirred over night at room temperature. The reaction was diluted with approx. 60 ml water and twice extracted with approx. 50 ml dichloromethane. The combined organic phases were extracted with brine, dried over sodium sulfate and concentrated to dryness under reduced pressure. The raw product was dissolved in dichloromethane and chromatographed over approx. 500 ml silica gel. Solvents used were dichloromethane, dichloromethane/methanol 40/1 and dichloromethane/methanol 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. The raw product was further purified by preparative RP-HPLC on a C18 column with a water/methanol gradient to yield 1.96 g (42% of theory) product.

Workup

  1. extractiontwice extracted with approx. 50 ml dichloromethane
  2. extractionThe combined organic phases were extracted with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness under reduced pressure
  5. dissolutionThe raw product was dissolved in dichloromethane
  6. customchromatographed over approx. 500 ml silica gel
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe raw product was further purified by preparative RP-HPLC on a C18 column with a water/methanol gradient
  9. customto yield 1.96 g (42% of theory) product

Sources & evidence

ORD record
ord-c29f398dcfe64ab0aa2fd3c1bc7de992
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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