Trifluoroacetic acid → (S)-2-amino-N-{(S)-1-[(S)-1-benzyl-2-((R)-2-methyl-oxiranyl)-2-oxo-ethylcarbamoyl]-2-difluoromethoxy-ethyl}-3-difluoromethoxy-propionamide TFA salt

HRID 61297Notes

Reaction equation

HRID 61297 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:14](=[O:39])[NH:15][C@H:16]([C:22](=[O:38])[NH:23][C@@H:24]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:25]([C@@:27]1([CH3:30])[CH2:29][O:28]1)=[O:26])[CH2:17][O:18][CH:19]([F:21])[F:20])[CH2:9][O:10][CH:11]([F:13])[F:12])(C)(C)C.[C:41]([OH:47])([C:43]([F:46])([F:45])[F:44])=[O:42]>ClCCl>[OH:47][C:41]([C:43]([F:46])([F:45])[F:44])=[O:42].[NH2:7][C@@H:8]([CH2:9][O:10][CH:11]([F:13])[F:12])[C:14]([NH:15][C@H:16]([C:22](=[O:38])[NH:23][C@@H:24]([CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:25]([C@@:27]1([CH3:30])[CH2:29][O:28]1)=[O:26])[CH2:17][O:18][CH:19]([F:20])[F:21])=[O:39]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90041239((S)-1-{(S)-1-[(S)-1-benzyl-2-((R)-2-methyl-oxiranyl)-2-oxo-ethylcarbamoyl]-2-difluoromethoxy-ethylcarbamoyl}-2-difluoromethoxy-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 131737165(S)-2-amino-N-{(S)-1-[(S)-1-benzyl-2-((R)-2-methyl-oxiranyl)-2-oxo-ethylcarbamoyl]-2-difluoromethoxy-ethyl}-3-difluoromethoxy-propionamide TFA saltYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the compound of Formula XIV(a), ((S)-1-{(S)-1-[(S)-1-benzyl-2-((R)-2-methyl-oxiranyl)-2-oxo-ethylcarbamoyl]-2-difluoromethoxy-ethylcarbamoyl}-2-difluoromethoxy-ethyl)-carbamic acid tert-butyl ester (2.68 g, 4.62 mmol) in dichloromethane (10 mL) at 0° C. was added TFA (10 mL), and the resulting mixture was stirred for 1 hr. Excess TFA was evaporated to dryness, and the residue obtained was triturated with ether in hexanes (2×20 mL) to provide the compound of Formula XV(a), (S)-2-amino-N—{(S)-1-[(S)-1-benzyl-2-((R)-2-methyl-oxiranyl)-2-oxo-ethylcarbamoyl]-2-difluoromethoxy-ethyl}-3-difluoromethoxy-propionamide TFA salt (2.34 g, 85%), as a pale-yellow solid. 1H NMR (300 MHz, d6-DMSO): δ (ppm) 7.42-7.32 (m, 3H), 7.23 (dd, 2H), 6.85 (wd, 1H), 6.71 (br s, 1H), 6.68 (wd, 1H), 6.10 (w t, 1H), 5.98 (wt, 1H), 5.12 (br s, 1H), 4.78 (td, 1H), 4.51 (td, 1H), 4.29 (m, 1H), 4.30-3.99 (m, 2H), 3.97 (dd, 1H), 3.85 (dd, 1H), 3.21 (d, 1H), 3.10 (dd, 1H), 2.86 (d, 1H), 2.81 (dd, 1H), 1.45 (s, 3H).

Workup

  1. customExcess TFA was evaporated to dryness
  2. customthe residue obtained
  3. customwas triturated with ether in hexanes (2×20 mL)

Sources & evidence

ORD record
ord-d75f2acdb78543539a0d91cd13039a16
Source dataset
uspto-grants-2016_09
Patent number
US09441012B2

Reaction notes

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