Triethylamine → HCID 11293464, compound

HRID 2054763Notes

Reaction equation

HRID 2054763 reaction equation
CC(C)([O-])C.[CH:6]1([C@H:9]([OH:31])[C:10]([N:12]2[CH2:16][C:15]([C:17]3[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=3[F:24])=[CH:14][C@H:13]2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:11])[CH2:8][CH2:7]1.C(N(CC)CC)C.[P:39](Cl)([O:43]C)([O:41]C)=[O:40]>ClCCl>[P:39]([OH:43])([OH:41])([O:31][C@@H:9]([CH:6]1[CH2:8][CH2:7]1)[C:10]([N:12]1[CH2:16][C:15]([C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])=[CH:14][C@H:13]1[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[O:11])=[O:40]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 101863Phosphorochloridic acid, dimethyl esterHCID 45749132-Methylpropan-2-olateHCID 24901497HCID 24901497, compound

Product 1

HCID 11293464HCID 11293464, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Titianium(IV) tert-butoxide (0.022 mL, 0.065 mmol, 0.100 equiv) was added to a solution of (1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethanol (6-2,230 mg, 0.647 mmol, 1 equiv) in dichloromethane (5 mL) at 23° C. followed by triethylamine (0.271 mL, 1.94 mmol, 3.00 equiv) and dimethyl chlorophosphate (0.140 mL, 1.29 mmol, 2.00 equiv). The resulting mixture was stirred for 2 h, then partitioned between saturated sodium bicarbonate solution (50 mL) and ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and were concentrated. The residue was dissolved in dimethyl sulfide (0.5 mL) and to the resulting solution was added methanesulfonic acid (1 mL). The resulting mixture was stirred for 10 min, then diluted with acetonitrile (3 mL). Purification by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) provided (1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethyl dihydrogen phosphate (10-1) as a white solid. 1H NMR (500 MHz, CDCl3) major rotamer: δ 7.42-7.04 (m, 8H), 6.46 (s, 1H), 5.95 (m, 1H), 5.14 (br d, 1H, J=14 Hz), 5.04 (br d, 1H, J=14 Hz), 4.46 (t, 1H, J=8.2 Hz), 1.32 (m, 1H), 0.62 (m, 4H). LRMS m/z (M+H) 436.4 found, 436.1 required.

Workup

  1. custompartitioned between saturated sodium bicarbonate solution (50 mL) and ethyl acetate (2×50 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationwere concentrated
  4. dissolutionThe residue was dissolved in dimethyl sulfide (0.5 mL) and to the resulting solution
  5. additionwas added methanesulfonic acid (1 mL)
  6. stirringThe resulting mixture was stirred for 10 min
  7. additiondiluted with acetonitrile (3 mL)
  8. customPurification by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record
ord-705ba04ad7c7415085765fcb8c013090
Source dataset
uspto-grants-2008_02
Patent number
US07329762B2

Reaction notes

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